Jump to content

Ribozyme

From Wikipedia, the free encyclopedia
(Redirected from Gene shears)
This article is about the chemical. For the rock band, see Ribozyme (band).
3D structure of a hammerhead ribozyme

Ribozymes (ribonucleic acid enzymes) are RNA molecules that have the ability to catalyze specific biochemical reactions, including RNA splicing in gene expression, similar to the action of protein enzymes. The 1982 discovery of ribozymes demonstrated that RNA can be both genetic material (like DNA) and a biological catalyst (like protein enzymes), and contributed to the RNA world hypothesis, which suggests that RNA may have been important in the evolution of prebiotic self-replicating systems.[1]

The most common activities of natural or in vitro evolved ribozymes are the cleavage (or ligation) of RNA and DNA and peptide bond formation.[2] For example, the smallest ribozyme known (GUGGC-3') can aminoacylate a GCCU-3' sequence in the presence of PheAMP.[3] Within the ribosome, ribozymes function as part of the large subunit ribosomal RNA to link amino acids during protein synthesis. They also participate in a variety of RNA processing reactions, including RNA splicing, viral replication, and transfer RNA biosynthesis. Examples of ribozymes include the hammerhead ribozyme, the VS ribozyme, leadzyme, and the hairpin ribozyme.

Researchers who are investigating the origins of life through the RNA world hypothesis have been working on discovering a ribozyme with the capacity to self-replicate, which would require it to have the ability to catalytically synthesize polymers of RNA. This should be able to happen in prebiotically plausible conditions with high rates of copying accuracy to prevent degradation of information but also allowing for the occurrence of occasional errors during the copying process to allow for Darwinian evolution to proceed.[4]

Attempts have been made to develop ribozymes as therapeutic agents, as enzymes which target defined RNA sequences for cleavage, as biosensors, and for applications in functional genomics and gene discovery.[5]

Discovery

[edit]
Schematic showing ribozyme cleavage of RNA

Before the discovery of ribozymes, enzymes—which were defined [solely] as catalytic proteins—were the only known biological catalysts. In 1967, Carl Woese, Francis Crick, and Leslie Orgel were the first to suggest that RNA could act as a catalyst. This idea was based upon the discovery that RNA can form complex secondary structures.[6] These ribozymes were found in the intron of an RNA transcript, which removed itself from the transcript, as well as in the RNA component of the RNase P complex, which is involved in the maturation of pre-tRNAs. In 1989, Thomas R. Cech and Sidney Altman shared the Nobel Prize in chemistry for their "discovery of catalytic properties of RNA".[7] The term ribozyme was first introduced by Kelly Kruger et al. in a paper published in Cell in 1982.[1]

It had been a firmly established belief in biology that catalysis was reserved for proteins. However, the idea of RNA catalysis is motivated in part by the old question regarding the origin of life: Which comes first, enzymes that do the work of the cell or nucleic acids that carry the information required to produce the enzymes? The concept of "ribonucleic acids as catalysts" circumvents this problem. RNA, in essence, can be both the chicken and the egg.[8]

In the 1980s, Thomas Cech, at the University of Colorado Boulder, was studying the excision of introns in a ribosomal RNA gene in Tetrahymena thermophila. While trying to purify the enzyme responsible for the splicing reaction, he found that the intron could be spliced out in the absence of any added cell extract. As much as they tried, Cech and his colleagues could not identify any protein associated with the splicing reaction. After much work, Cech proposed that the intron sequence portion of the RNA could break and reform phosphodiester bonds. At about the same time, Sidney Altman, a professor at Yale University, was studying the way tRNA molecules are processed in the cell when he and his colleagues isolated an enzyme called RNase-P, which is responsible for conversion of a precursor tRNA into the active tRNA. Much to their surprise, they found that RNase-P contained RNA in addition to protein and that RNA was an essential component of the active enzyme. This was such a foreign idea that they had difficulty publishing their findings. The following year[which?], Altman demonstrated that RNA can act as a catalyst by showing that the RNase-P RNA subunit could catalyze the cleavage of precursor tRNA into active tRNA in the absence of any protein component.

Since Cech's and Altman's discovery, other investigators have discovered other examples of self-cleaving RNA or catalytic RNA molecules. Many ribozymes have either a hairpin – or hammerhead – shaped active center and a unique secondary structure that allows them to cleave other RNA molecules at specific sequences. It is now possible to make ribozymes that will specifically cleave any RNA molecule. These RNA catalysts may have pharmaceutical applications. For example, a ribozyme has been designed to cleave the RNA of HIV. If such a ribozyme were made by a cell, all incoming virus particles would have their RNA genome cleaved by the ribozyme, which would prevent infection.

Structure and mechanism

[edit]

Despite having only four choices for each monomer unit (nucleotides), compared to 20 amino acid side chains found in proteins, ribozymes have diverse structures and mechanisms. In many cases they are able to mimic the mechanism used by their protein counterparts. For example, in self cleaving ribozyme RNAs, an in-line SN2 reaction is carried out using the 2’ hydroxyl group as a nucleophile attacking the bridging phosphate and causing 5’ oxygen of the N+1 base to act as a leaving group. In comparison, RNase A, a protein that catalyzes the same reaction, uses a coordinating histidine and lysine to act as a base to attack the phosphate backbone.[2][clarification needed]

Like many protein enzymes, metal binding is also critical to the function of many ribozymes.[9] Often these interactions use both the phosphate backbone and the base of the nucleotide, causing drastic conformational changes.[10] There are two mechanism classes for the cleavage of a phosphodiester backbone in the presence of metal. In the first mechanism, the internal 2’- OH group attacks the phosphorus center in a SN2 mechanism. Metal ions promote this reaction by first coordinating the phosphate oxygen and later stabling the oxyanion. The second mechanism also follows a SN2 displacement, but the nucleophile comes from water or exogenous hydroxyl groups rather than RNA itself. The smallest ribozyme is UUU, which can promote the cleavage between G and A of the GAAA tetranucleotide via the first mechanism in the presence of Mn2+. The reason why this trinucleotide (rather than the complementary tetramer) catalyzes this reaction may be because the UUU-AAA pairing is the weakest and most flexible trinucleotide among the 64 conformations, which provides the binding site for Mn2+.[11]

Phosphoryl transfer can also be catalyzed without metal ions. For example, pancreatic ribonuclease A and hepatitis delta virus (HDV) ribozymes can catalyze the cleavage of RNA backbone through acid-base catalysis without metal ions.[12][13] Hairpin ribozyme can also catalyze the self-cleavage of RNA without metal ions, but the mechanism for this is still unclear.[13]

Ribozyme can also catalyze the formation of peptide bond between adjacent amino acids by lowering the activation entropy.[12]

Ribozyme structure pictures
Image showing the diversity of ribozyme structures. From left to right: leadzyme, hammerhead ribozyme, twister ribozyme

Activities

[edit]
A ribosome is a biological machine that utilizes a ribozyme to translate RNA into proteins.

Although ribozymes are quite rare in most cells, their roles are sometimes essential to life. For example, the functional part of the ribosome, the biological machine that translates RNA into proteins, is fundamentally a ribozyme, composed of RNA tertiary structural motifs that are often coordinated to metal ions such as Mg2+ as cofactors.[14] In a model system, there is no requirement for divalent cations in a five-nucleotide RNA catalyzing trans-phenylalanation of a four-nucleotide substrate with 3 base pairs complementary with the catalyst, where the catalyst/substrate were devised by truncation of the C3 ribozyme.[15]

The best-studied ribozymes are probably those that cut themselves or other RNAs, as in the original discovery by Cech[16] and Altman.[17] However, ribozymes can be designed to catalyze a range of reactions, many of which may occur in life but have not been discovered in cells.[18]

RNA may catalyze folding of the pathological protein conformation of a prion in a manner similar to that of a chaperonin.[19]

Ribozymes and the origin of life

[edit]

RNA can also act as a hereditary molecule, which encouraged Walter Gilbert to propose that in the distant past, the cell used RNA as both the genetic material and the structural and catalytic molecule rather than dividing these functions between DNA and protein as they are today; this hypothesis is known as the "RNA world hypothesis" of the origin of life.[20] Since nucleotides and RNA (and thus ribozymes) can arise by inorganic chemicals, they are candidates for the first enzymes, and in fact, the first "replicators" (i.e., information-containing macro-molecules that replicate themselves). An example of a self-replicating ribozyme that ligates two substrates to generate an exact copy of itself was described in 2002.[21] The discovery of the catalytic activity of RNA solved the "chicken and egg" paradox of the origin of life, solving the problem of origin of peptide and nucleic acid central dogma. According to this scenario, at the origin of life, all enzymatic activity and genetic information encoding was done by one molecule: RNA.

Ribozymes have been produced in the laboratory that are capable of catalyzing the synthesis of other RNA molecules from activated monomers under very specific conditions, these molecules being known as RNA polymerase ribozymes.[22] The first RNA polymerase ribozyme was reported in 1996, and was capable of synthesizing RNA polymers up to 6 nucleotides in length.[23] Mutagenesis and selection has been performed on an RNA ligase ribozyme from a large pool of random RNA sequences,[24] resulting in isolation of the improved "Round-18" polymerase ribozyme in 2001 which could catalyze RNA polymers now up to 14 nucleotides in length.[25] Upon application of further selection on the Round-18 ribozyme, the B6.61 ribozyme was generated and was able to add up to 20 nucleotides to a primer template in 24 hours, until it decomposes by cleavage of its phosphodiester bonds.[26]

The rate at which ribozymes can polymerize an RNA sequence multiples substantially when it takes place within a micelle.[27]

The next ribozyme discovered was the "tC19Z" ribozyme, which can add up to 95 nucleotides with a fidelity of 0.0083 mutations/nucleotide.[28] Next, the "tC9Y" ribozyme was discovered by researchers and was further able to synthesize RNA strands up to 206 nucleotides long in the eutectic phase conditions at below-zero temperature,[29] conditions previously shown to promote ribozyme polymerase activity.[30]

The RNA polymerase ribozyme (RPR) called tC9-4M was able to polymerize RNA chains longer than itself (i.e. longer than 177 nt) in magnesium ion concentrations close to physiological levels, whereas earlier RPRs required prebiotically implausible concentrations of up to 200 mM. The only factor required for it to achieve this was the presence of a very simple amino acid polymer called lysine decapeptide.[31]

The most complex RPR synthesized by that point was called 24-3, which was newly capable of polymerizing the sequences of a substantial variety of nucleotide sequences and navigating through complex secondary structures of RNA substrates inaccessible to previous ribozymes. In fact, this experiment was the first to use a ribozyme to synthesize a tRNA molecule.[32] Starting with the 24-3 ribozyme, Tjhung et al.[33] applied another fourteen rounds of selection to obtain an RNA polymerase ribozyme by in vitro evolution termed '38-6' that has an unprecedented level of activity in copying complex RNA molecules. However, this ribozyme is unable to copy itself and its RNA products have a high mutation rate. In a subsequent study, the researchers began with the 38-6 ribozyme and applied another 14 rounds of selection to generate the '52-2' ribozyme, which compared to 38-6, was again many times more active and could begin generating detectable and functional levels of the class I ligase, although it was still limited in its fidelity and functionality in comparison to copying of the same template by proteins such as the T7 RNA polymerase.[34]

An RPR called t5(+1) adds triplet nucleotides at a time instead of just one nucleotide at a time. This heterodimeric RPR can navigate secondary structures inaccessible to 24-3, including hairpins. In the initial pool of RNA variants derived only from a previously synthesized RPR known as the Z RPR, two sequences separately emerged and evolved to be mutualistically dependent on each other. The Type 1 RNA evolved to be catalytically inactive, but complexing with the Type 5 RNA boosted its polymerization ability and enabled intermolecular interactions with the RNA template substrate obviating the need to tether the template directly to the RNA sequence of the RPR, which was a limitation of earlier studies. Not only did t5(+1) not need tethering to the template, but a primer was not needed either as t5(+1) had the ability to polymerize a template in both 3' → 5' and 5' 3 → 3' directions.[35]

A highly evolved[vague] RNA polymerase ribozyme was able to function as a reverse transcriptase, that is, it can synthesize a DNA copy using an RNA template.[36] Such an activity is considered[by whom?] to have been crucial for the transition from RNA to DNA genomes during the early history of life on earth. Reverse transcription capability could have arisen as a secondary function of an early RNA-dependent RNA polymerase ribozyme.

An RNA sequence that folds into a ribozyme is capable of invading duplexed RNA, rearranging into an open holopolymerase complex, and then searching for a specific RNA promoter sequence, and upon recognition rearrange again into a processive form that polymerizes a complementary strand of the sequence. This ribozyme is capable of extending duplexed RNA by up to 107 nucleotides, and does so without needing to tether the sequence being polymerized.[37]

Artificial ribozymes

[edit]

Since the discovery of ribozymes that exist in living organisms, there has been interest in the study of new synthetic ribozymes made in the laboratory. For example, artificially produced self-cleaving RNAs with good enzymatic activity have been produced. Tang and Breaker[38] isolated self-cleaving RNAs by in vitro selection of RNAs originating from random-sequence RNAs. Some of the synthetic ribozymes that were produced had novel structures, while some were similar to the naturally occurring hammerhead ribozyme.

In 2015, researchers at Northwestern University and the University of Illinois Chicago engineered a tethered ribosome that works nearly as well as the authentic cellular component that produces all the proteins and enzymes within the cell. Called Ribosome-T, or Ribo-T, the artificial ribosome was created by Michael Jewett and Alexander Mankin.[39] The techniques used to create artificial ribozymes involve directed evolution. This approach takes advantage of RNA's dual nature as both a catalyst and an informational polymer, making it easy for an investigator to produce vast populations of RNA catalysts using polymerase enzymes. The ribozymes are mutated by reverse transcribing them with reverse transcriptase into various cDNA and amplified with error-prone PCR. The selection parameters in these experiments often differ. One approach for selecting a ligase ribozyme involves using biotin tags, which are covalently linked to the substrate. If a molecule possesses the desired ligase activity, a streptavidin matrix can be used to recover the active molecules.

Lincoln and Joyce used in vitro evolution to develop ribozyme ligases capable of self-replication in about an hour, via the joining of pre-synthesized highly complementary oligonucleotides.[40]

Although not true catalysts, the creation of artificial self-cleaving riboswitches, termed aptazymes, has also been an active area of research. Riboswitches are regulatory RNA motifs that change their structure in response to a small molecule ligand to regulate translation. While there are many known natural riboswitches that bind a wide array of metabolites and other small organic molecules, only one ribozyme based on a riboswitch has been described: glmS.[41] Early work in characterizing self-cleaving riboswitches was focused on using theophylline as the ligand. In these studies, an RNA hairpin is formed which blocks the ribosome binding site, thus inhibiting translation. In the presence of the ligand, in these cases theophylline, the regulatory RNA region is cleaved off, allowing the ribosome to bind and translate the target gene. Much of this RNA engineering work was based on rational design and previously determined RNA structures rather than directed evolution as in the above examples. More recent work has broadened the ligands used in ribozyme riboswitches to include thymine pyrophosphate. Fluorescence-activated cell sorting has also been used to engineering aptazymes.[42]

Applications

[edit]

Ribozymes have been proposed and developed for the treatment of disease through gene therapy. One major challenge of using RNA-based enzymes as a therapeutic is the short half-life of the catalytic RNA molecules in the body. To combat this, the 2’ position on the ribose is modified to improve RNA stability. One area of ribozyme gene therapy has been the inhibition of RNA-based viruses.

A type of synthetic ribozyme directed against HIV RNA called gene shears has been developed and has entered clinical testing for HIV infection.[43][44]

Similarly, ribozymes have been designed to target the hepatitis C virus RNA, SARS coronavirus (SARS-CoV),[45] Adenovirus[45] and influenza A and B virus RNA.[46][47][48][45] The ribozyme is able to cleave the conserved regions of the virus's genome, which has been shown to reduce the virus in mammalian cell culture.[49] Despite these efforts by researchers, these projects have remained in the preclinical stage.

Known ribozymes

[edit]

Well-validated naturally occurring ribozyme classes:

See also

[edit]

Notes and references

[edit]
  1. ^ a b Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR (November 1982). "Self-splicing RNA: autoexcision and autocyclization of the ribosomal RNA intervening sequence of Tetrahymena". Cell. 31 (1): 147–157. doi:10.1016/0092-8674(82)90414-7. PMID 6297745. S2CID 14787080.
  2. ^ a b Fedor MJ, Williamson JR (May 2005). "The catalytic diversity of RNAs". Nature Reviews. Molecular Cell Biology. 6 (5): 399–412. doi:10.1038/nrm1647. PMID 15956979. S2CID 33304782.
  3. ^ Yarus M (October 2011). "The meaning of a minuscule ribozyme". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 366 (1580): 2902–2909. doi:10.1098/rstb.2011.0139. PMC 3158920. PMID 21930581.
  4. ^ Martin LL, Unrau PJ, Müller UF (January 2015). "RNA synthesis by in vitro selected ribozymes for recreating an RNA world". Life. 5 (1). Basel, Switzerland: 247–68. Bibcode:2015Life....5..247M. doi:10.3390/life5010247. PMC 4390851. PMID 25610978.
  5. ^ Hean J, Weinberg MS (2008). "The Hammerhead Ribozyme Revisited: New Biological Insights for the Development of Therapeutic Agents and for Reverse Genomics Applications". In Morris KL (ed.). RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity. Norfolk, England: Caister Academic Press. ISBN 978-1-904455-25-7.
  6. ^ Woese C (1967). The Genetic Code. New York: Harper and Row.
  7. ^ The Nobel Prize in Chemistry 1989 was awarded to Thomas R. Cech and Sidney Altman "for their discovery of catalytic properties of RNA".
  8. ^ Visser CM (1984). "Evolution of biocatalysis 1. Possible pre-genetic-code RNA catalysts which are their own replicase". Origins of Life. 14 (1–4): 291–300. Bibcode:1984OrLi...14..291V. doi:10.1007/BF00933670. PMID 6205343. S2CID 31409366.
  9. ^ Pyle AM (August 1993). "Ribozymes: a distinct class of metalloenzymes". Science. 261 (5122): 709–714. Bibcode:1993Sci...261..709P. doi:10.1126/science.7688142. PMID 7688142.
  10. ^ Freisinger E, Sigel RK (2007). "From nucleotides to ribozymes—A comparison of their metal ion binding properties" (PDF). Coord. Chem. Rev. 251 (13–14): 1834–1851. doi:10.1016/j.ccr.2007.03.008.
  11. ^ Pyle AM (August 1993). "Ribozymes: a distinct class of metalloenzymes". Science. 261 (5122): 709–714. Bibcode:1993Sci...261..709P. doi:10.1126/science.7688142. JSTOR 2882234. PMID 7688142.
  12. ^ a b Lilley DM (October 2011). "Mechanisms of RNA catalysis". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 366 (1580): 2910–2917. doi:10.1098/rstb.2011.0132. JSTOR 23035661. PMC 3158914. PMID 21930582.
  13. ^ a b Doudna JA, Cech TR (July 2002). "The chemical repertoire of natural ribozymes". Nature. 418 (6894): 222–228. Bibcode:2002Natur.418..222D. doi:10.1038/418222a. PMID 12110898. S2CID 4417095.
  14. ^ Ban N, Nissen P, Hansen J, Moore PB, Steitz TA (August 2000). "The complete atomic structure of the large ribosomal subunit at 2.4 A resolution". Science. 289 (5481): 905–920. Bibcode:2000Sci...289..905B. CiteSeerX 10.1.1.58.2271. doi:10.1126/science.289.5481.905. PMID 10937989.
  15. ^ Turk RM, Chumachenko NV, Yarus M (March 2010). "Multiple translational products from a five-nucleotide ribozyme". Proceedings of the National Academy of Sciences of the United States of America. 107 (10): 4585–4589. Bibcode:2010PNAS..107.4585T. doi:10.1073/pnas.0912895107. PMC 2826339. PMID 20176971.
  16. ^ Cech TR (August 2000). "Structural biology. The ribosome is a ribozyme". Science. 289 (5481): 878–879. doi:10.1126/science.289.5481.878. PMID 10960319. S2CID 24172338.
  17. ^ Altman S (August 1990). "Nobel lecture. Enzymatic cleavage of RNA by RNA". Bioscience Reports. 10 (4): 317–337. doi:10.1007/BF01117232. PMID 1701103. S2CID 12733970.
  18. ^ Walter NG, Engelke DR (October 2002). "Ribozymes: catalytic RNAs that cut things, make things, and do odd and useful jobs". Biologist. 49 (5): 199–203. PMC 3770912. PMID 12391409.
  19. ^ Supattapone S (June 2004). "Prion protein conversion in vitro". Journal of Molecular Medicine. 82 (6): 348–356. doi:10.1007/s00109-004-0534-3. PMID 15014886. S2CID 24908667.
  20. ^ Gilbert W (1986). "Origin of life: The RNA world". Nature. 319 (6055): 618. Bibcode:1986Natur.319..618G. doi:10.1038/319618a0. S2CID 8026658.
  21. ^ Paul N, Joyce GF (October 2002). "A self-replicating ligase ribozyme". Proceedings of the National Academy of Sciences of the United States of America. 99 (20): 12733–12740. Bibcode:2002PNAS...9912733P. doi:10.1073/pnas.202471099. PMC 130529. PMID 12239349.
  22. ^ Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP (May 2001). "RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension". Science. 292 (5520): 1319–1325. Bibcode:2001Sci...292.1319J. CiteSeerX 10.1.1.70.5439. doi:10.1126/science.1060786. PMID 11358999. S2CID 14174984.
  23. ^ Ekland EH, Bartel DP (July 1996). "RNA-catalysed RNA polymerization using nucleoside triphosphates". Nature. 382 (6589): 373–6. Bibcode:1996Natur.382..373E. doi:10.1038/382373a0. PMID 8684470. S2CID 4367137.
  24. ^ Bartel DP, Szostak JW (September 1993). "Isolation of new ribozymes from a large pool of random sequences [see comment]". Science. 261 (5127). New York, N.Y.: 1411–8. doi:10.1126/science.7690155. PMID 7690155.
  25. ^ Johnston WK, Unrau PJ, Lawrence MS, Glasner ME, Bartel DP (May 2001). "RNA-catalyzed RNA polymerization: accurate and general RNA-templated primer extension". Science. 292 (5520). New York, N.Y.: 1319–25. Bibcode:2001Sci...292.1319J. doi:10.1126/science.1060786. PMID 11358999. S2CID 14174984.
  26. ^ Zaher HS, Unrau PJ (July 2007). "Selection of an improved RNA polymerase ribozyme with superior extension and fidelity". RNA. 13 (7): 1017–1026. doi:10.1261/rna.548807. PMC 1894930. PMID 17586759.
  27. ^ Müller UF, Bartel DP (March 2008). "Improved polymerase ribozyme efficiency on hydrophobic assemblies". RNA. 14 (3). New York, N.Y.: 552–62. doi:10.1261/rna.494508. PMC 2248263. PMID 18230767.
  28. ^ Wochner A, Attwater J, Coulson A, Holliger P (April 2011). "Ribozyme-catalyzed transcription of an active ribozyme". Science. 332 (6026): 209–212. Bibcode:2011Sci...332..209W. doi:10.1126/science.1200752. PMID 21474753. S2CID 39990861.
  29. ^ Attwater J, Wochner A, Holliger P (December 2013). "In-ice evolution of RNA polymerase ribozyme activity". Nature Chemistry. 5 (12): 1011–8. Bibcode:2013NatCh...5.1011A. doi:10.1038/nchem.1781. PMC 3920166. PMID 24256864.
  30. ^ Attwater J, Wochner A, Pinheiro VB, Coulson A, Holliger P (September 2010). "Ice as a protocellular medium for RNA replication". Nature Communications. 1 (6): 76. Bibcode:2010NatCo...1...76A. doi:10.1038/ncomms1076. PMID 20865803.
  31. ^ Tagami S, Attwater J, Holliger P (April 2017). "Simple peptides derived from the ribosomal core potentiate RNA polymerase ribozyme function". Nature Chemistry. 9 (4): 325–332. Bibcode:2017NatCh...9..325T. doi:10.1038/nchem.2739. PMC 5458135. PMID 28338682.
  32. ^ Horning DP, Joyce GF (August 2016). "Amplification of RNA by an RNA polymerase ribozyme". Proceedings of the National Academy of Sciences of the United States of America. 113 (35): 9786–91. Bibcode:2016PNAS..113.9786H. doi:10.1073/pnas.1610103113. PMC 5024611. PMID 27528667.
  33. ^ Tjhung KF, Shokhirev MN, Horning DP, Joyce GF (February 2020). "An RNA polymerase ribozyme that synthesizes its own ancestor". Proceedings of the National Academy of Sciences of the United States of America. 117 (6): 2906–2913. Bibcode:2020PNAS..117.2906T. doi:10.1073/pnas.1914282117. PMC 7022166. PMID 31988127.
  34. ^ Portillo X, Huang YT, Breaker RR, Horning DP, Joyce GF (2021). "Witnessing the structural evolution of an RNA enzyme". eLife. 10: e71557. doi:10.7554/eLife.71557. PMC 8460264. PMID 34498588.
  35. ^ Attwater J, Raguram A, Morgunov AS, Gianni E, Holliger P (May 2018). "Ribozyme-catalysed RNA synthesis using triplet building blocks". eLife. 7. doi:10.7554/eLife.35255. PMC 6003772. PMID 29759114.
  36. ^ Samanta B, Joyce GF (September 2017). "A reverse transcriptase ribozyme". eLife. 6. doi:10.7554/eLife.31153. PMC 5665644. PMID 28949294.
  37. ^ Cojocaru R, Unrau PJ (March 2021). "Processive RNA polymerization and promoter recognition in an RNA World". Science. 371 (6535): 1225–1232. Bibcode:2021Sci...371.1225C. doi:10.1126/science.abd9191. PMID 33737482. S2CID 232271298.
  38. ^ Tang J, Breaker RR (May 2000). "Structural diversity of self-cleaving ribozymes". Proceedings of the National Academy of Sciences of the United States of America. 97 (11): 5784–5789. Bibcode:2000PNAS...97.5784T. doi:10.1073/pnas.97.11.5784. PMC 18511. PMID 10823936.
  39. ^ Engineer and Biologist Design First Artificial Ribosome - Designer ribosome could lead to new drugs and next-generation biomaterials published on July 31, 2015 by Northwestern University
  40. ^ Lincoln TA, Joyce GF (February 2009). "Self-sustained replication of an RNA enzyme". Science. 323 (5918): 1229–1232. Bibcode:2009Sci...323.1229L. doi:10.1126/science.1167856. PMC 2652413. PMID 19131595.
  41. ^ Winkler WC, Nahvi A, Roth A, Collins JA, Breaker RR (March 2004). "Control of gene expression by a natural metabolite-responsive ribozyme". Nature. 428 (6980): 281–286. Bibcode:2004Natur.428..281W. doi:10.1038/nature02362. PMID 15029187. S2CID 4301164.
  42. ^ Lynch SA, Gallivan JP (January 2009). "A flow cytometry-based screen for synthetic riboswitches". Nucleic Acids Research. 37 (1): 184–192. doi:10.1093/nar/gkn924. PMC 2615613. PMID 19033367.
  43. ^ de Feyter R, Li P (June 2000). "Technology evaluation: HIV ribozyme gene therapy, Gene Shears Pty Ltd". Current Opinion in Molecular Therapeutics. 2 (3): 332–335. PMID 11249628.
  44. ^ Khan AU (May 2006). "Ribozyme: a clinical tool". Clinica Chimica Acta; International Journal of Clinical Chemistry. 367 (1–2): 20–27. doi:10.1016/j.cca.2005.11.023. PMID 16426595.
  45. ^ a b c Asha K, Kumar P, Sanicas M, Meseko CA, Khanna M, Kumar B (December 2018). "Advancements in Nucleic Acid Based Therapeutics against Respiratory Viral Infections". Journal of Clinical Medicine. 8 (1): 6. doi:10.3390/jcm8010006. PMC 6351902. PMID 30577479.
  46. ^ Khanna M, Saxena L, Rajput R, Kumar B, Prasad R (2015). "Gene silencing: a therapeutic approach to combat influenza virus infections". Future Microbiology. 10 (1): 131–140. doi:10.2217/fmb.14.94. PMID 25598342.
  47. ^ Kumar B, Khanna M, Kumar P, Sood V, Vyas R, Banerjea AC (May 2012). "Nucleic acid-mediated cleavage of M1 gene of influenza A virus is significantly augmented by antisense molecules targeted to hybridize close to the cleavage site". Molecular Biotechnology. 51 (1): 27–36. doi:10.1007/s12033-011-9437-z. PMID 21744034. S2CID 45686564.
  48. ^ Kumar B, Asha K, Khanna M, Ronsard L, Meseko CA, Sanicas M (April 2018). "The emerging influenza virus threat: status and new prospects for its therapy and control". Archives of Virology. 163 (4): 831–844. doi:10.1007/s00705-018-3708-y. PMC 7087104. PMID 29322273.
  49. ^ Lieber A, He CY, Polyak SJ, Gretch DR, Barr D, Kay MA (December 1996). "Elimination of hepatitis C virus RNA in infected human hepatocytes by adenovirus-mediated expression of ribozymes". Journal of Virology. 70 (12): 8782–8791. doi:10.1128/JVI.70.12.8782-8791.1996. PMC 190975. PMID 8971007.
  50. ^ Nielsen H, Westhof E, Johansen S (September 2005). "An mRNA is capped by a 2', 5' lariat catalyzed by a group I-like ribozyme". Science. 309 (5740): 1584–1587. Bibcode:2005Sci...309.1584N. doi:10.1126/science.1113645. PMID 16141078. S2CID 37002071.
  51. ^ Fica SM, Tuttle N, Novak T, Li NS, Lu J, Koodathingal P, et al. (November 2013). "RNA catalyses nuclear pre-mRNA splicing". Nature. 503 (7475): 229–234. Bibcode:2013Natur.503..229F. doi:10.1038/nature12734. PMC 4666680. PMID 24196718.

Further reading

[edit]
[edit]
Retrieved from "https://en.wikipedia.org/w/index.php?title=Ribozyme&oldid=1249360499#Applications"