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THE FREQUENCY AND FITNESS OF m6A-ASSOCIATED VARIANTS COULD BE MODULATED BY THE THERMODYNAMIC STABILITY OF AN OVERLAPPING G-QUADRUPLEX

Year 2023, Volume: 6 Issue: 3, 219 - 228, 24.10.2023

Çağrı Güleç

https://doi.org/10.26650/JARHS2023-1349345

Abstract

Objective: Post-transcriptional modifications like m6A (N6-methyladenosine) and secondary structures like G-quadruplex (G4) are formations that play a vital role in RNA processing. Their synergy also has functional consequences. Since m6A is known to be enzymatically created in the DRACH-motif, and that genetic variants can create a novel DRACH-motif or abolish a pre-existing DRACH-motif, we can hypothesize that variants which affect the gene product level through modulating m6A-G4 colocalization, may also consequently affect fitness and change the allele frequency. To test this hypothesis, the rare and common variants in selected human genes were investigated to determine their effect on DRACH-G4 colocalization.
Material and Methods: Genomic sequences and variant information were retrieved from the GRCh37/hg19 and Biomart-Ensembl databases. Experimentally determined G4 sequences were obtained from two different studies.
Results: Common variants leading to the formation of a novel DRACHmotif were found to be significantly higher inside the G4 structure than outside. In contrast, rare variants with the same feature were higher outside the G4-structure and had uneven distribution alongside the premRNA. The uneven distribution of the DRACH-creating rare variants was observed to correlate with their effect on thermodynamic stability of the overlapping G4.
Conclusion: Selective DRACH-G4 colocalization suggests that m6A is evolutionally favorable when overlapping with G4. The thermodynamic stability could lead to uneven distribution of DRACH-G4 colocalization, favorable in 3-prime-side, but not in 5-prime-side. We can conclude that the fitness, and consequently frequency of a DRACH-creating variant is prone to become higher or lower depending in its position and effect on the overlapping-G4 stability.

Keywords

RNA modification N6-methyladenosine G-quadruplex allele frequency

References

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  • 4- Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012;485(7397):201-6. google scholar
  • 5- Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Comprehensive analysis of mRNA methylation reveals enrichment in 30 UTRs and near stop codons. Cell 2012;149(7); 1635-46. google scholar
  • 6- Roundtree IA, Evans ME, Pan T, He C. Dynamic RNA modifications in gene expression regulation. Cell 2017;169(7):1187-200. google scholar
  • 7- Zhao BS, Roundtree IA, He C. Post-transcriptional gene regulation by mRNA modifications. Nat Rev Mol Cell Biol 2017;18(1):31-42. google scholar
  • 8- Shi H, Wang X, Lu Z, Zhao BS, Ma H, Hsu PJ, et al. YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA. Cell Res 2017;27(3):315-28. google scholar
  • 9- Roignant JY, Soller M. m6A in mRNA: an ancient mechanism for fine-tuning gene expression. Trends Genet 2017;33(6):380-90. google scholar
  • 10- Gilbert WV, Bell TA, Schaening C. Messenger RNA modifications: form, distribution, and function. Science 2016;352(6292):1408-12. google scholar
  • 11- Bochman ML, Paeschke K, Zakian VA. DNA secondary structures: stability and function of G-quadruplex structures. Nat Rev Genet 2012;13(11):770-80. google scholar
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  • 13- Rachwal PA, Fox KR. Quadruplex melting. Methods 2007;43(4):291-301. google scholar
  • 14- Rachwal PA, Brown T, Fox KR. Sequence effects of single base loops in intramolecular quadruplex DNA. FEBS Lett 2007;581(8):1657-60. google scholar
  • 15- Mukundan VT, Phan AT. Bulges in G-quadruplexes: broadening the definition of G-quadruplex-forming sequences. J Am Chem Soc 2013;135(13):5017-28. google scholar
  • 16- Lam EY, Beraldi D, Tannahill D, Balasubramanian S. G-quadruplex structures are stable and detectable in human genomic DNA. Nat Commun 2013;4:1796. google scholar
  • 17- Bugaut A, Murat P, Balasubramanian S. An RNA hairpin to G-quadruplex conformational transition. J Am Chem Soc 2012;134(49):19953-6. google scholar
  • 18- Huppert JL, Balasubramanian S. G-quadruplexes in promoters throughout the human genome. Nucleic Acids Res 2007;35(2):406-13. google scholar
  • 19- Huppert JL. Hunting G-quadruplexes. Biochimie 2008;90(8):1140-8. google scholar
  • 20- Kumari S, Bugaut A, Huppert JL, Balasubramanian S. An RNA G-quadruplex in the 5’ UTR of the NRAS proto-oncogene modulates translation. Nat Chem Biol 2007;3(4):218-21. google scholar
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  • 22- Huppert JL, Bugaut A, Kumari S, Balasubramanian S. G-quadruplexes: the beginning and end of UTRs. Nucleic Acids Res 2008;36(19):6260-8. google scholar
  • 23- Thandapani P, Song J, Gandin V, Cai Y, Rouleau SG, Garant JM, et al. Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes. Elife 2015;4:e06234. google scholar
  • 24- Brazda V, Haronı'kova L, Liao JC, Fojta M. DNA and RNA quadruplex-binding proteins. Int J Mol Sci 2014;15(10):17493-517. google scholar
  • 25- Lyons SM, Kharel P, Akiyama Y, Ojha S, Dave D, Tsvetkov V, et al. eIF4G has intrinsic G-quadruplex binding activity that is required for tiRNA function. Nucleic Acids Res 2020;48(11):6223-33. google scholar
  • 26- Niu K, Xiang L, Jin Y, Peng Y, Wu F, Tang W, et al. Identification of LARK as a novel and conserved G-quadruplex binding protein in invertebrates and vertebrates. Nucleic Acids Res 2019;47(14):7306-20. google scholar
  • 27- Williams P, Li L, Dong X, Wang Y. Identification of SLIRP as a G Quadruplex-Binding Protein. J Am Chem Soc 2017;139(36):12426-9. google scholar
  • 28- Serikawa T, Spanos C, von Hacht A, Budisa N, Rappsilber J, Kurreck J. Comprehensive identification of proteins binding to RNA G-quadruplex motifs in the 5’ UTR of tumor-associated mRNAs. Biochimie 2018;144:169-84. google scholar
  • 29- Lyonnais S, Tarres-Sole A, Rubio-Cosials A, Cuppari A, Brito R, Jaumot J, et al. The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein. Sci Rep 2017;7:43992. google scholar
  • 30- Khateb S, Weisman-Shomer P, Hershco-Shani I, Ludwig AL, Fry M. The tetraplex (CGG)n destabilizing proteins hnRNP A2 and CBF-A enhance the in vivo translation of fragile X premutation mRNA. Nucleic Acids Res 2007;35(17):5775-88. google scholar
  • 31- Yang X, Liu QL, Xu W, Zhang YC, Yang Y, Ju LF, et al. m6A promotes R-loop formation to facilitate transcription termination. Cell Res 2019;29(12):1035-8. google scholar
  • 32- Abakir A, Giles TC, Cristini A, Foster JM, Dai N, Starczak M, et al. N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nat Genet 2020;52(1):48-55. google scholar
  • 33- Jara-Espejo M, Fleming AM, Burrows CJ. potential G-quadruplex forming sequences and N6-methyladenosine colocalize at human Pre-mRNA intron splice sites. ACS Chem Biol 2020;15(6):1292-130. google scholar
  • 34- Fleming AM, Nguyen NLB, Burrows CJ. colocalization of m6A and G-Quadruplex-Forming sequences in Viral RNA (HIV, Zika, hepatitis B, and SV40) suggests topological control of adenosine N6-methylation. ACS Cent Sci 2019;5(2):218-28. google scholar
  • 35- Kwok CK, Marsico G, Sahakyan AB, Chambers VS, Balasubramanian S. rG4-seq reveals widespread formation of G-quadruplex structures in the human transcriptome. Nat Methods 2016;13(10):841-4. google scholar
  • 36- Hui WWI, Simeone A, Zyner KG, Tannahill D, Balasubramanian S. Single-cell mapping of DNA G-quadruplex structures in human cancer cells. Sci Rep 2021;11(1):23641. google scholar
  • 37- Csepany T, Lin A, Baldick CJ Jr, Beemon K. Sequence specificity of mRNA N6-adenosine methyltransferase. J Biol Chem 1990;265(33):20117-22. google scholar
  • 38- Bushkin GG, Pincus D, Morgan JT, Richardson K, Lewis C, Chan SH, et al. m6A modification of a 3’ UTR site reduces RME1 mRNA levels to promote meiosis. Nat Commun 2019;10(1):3414. google scholar
  • 39- Batista PJ, Molinie B, Wang J, Qu K, Zhang J, Li L, et al. m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 2014;15(6):707-19. google scholar
  • 40- Rouleau S, Glouzon JS, Brumwell A, Bisaillon M, Perreault JP. 3’ UTR G-quadruplexes regulate miRNA binding. RNA 2017;23(8):1172-9. google scholar
  • 41- Jodoin R, Carrier JC, Rivard N, Bisaillon M, Perreault JP. G-quadruplex located in the 5’UTR of the BAG-1 mRNA affects both its cap-dependent and cap-independent translation through global secondary structure maintenance. Nucleic Acids Res 2019;47(19):10247-66. google scholar
  • 42- Song J, Perreault JP, Topisirovic I, Richard S. RNA G-quadruplexes and their potential regulatory roles in translation. Translation (Austin) 2016;4(2):e1244031. google scholar
  • 43- von Hacht A, Seifert O, Menger M, Schütze T, Arora A, Konthur Z, et al. Identification and characterization of RNA guanine-quadruplex binding proteins. Nucleic Acids Res 2014;42(10):6630-44. google scholar
  • 44- Roundtree IA, He C. Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. Trends Genet 2016;32(6):320-1. google scholar
  • 45- Xue Y, Liu JQ, Zheng KW, Kan ZY, Hao YH, Tan Z. Kinetic and thermodynamic control of G-quadruplex folding. Angew Chem Int Ed Engl 2011;50(35):8046-50. google scholar
  • 46- Song Y, Xu Q, Wei Z, Zhen D, Su J, Chen K, Meng J. Predict Epitranscriptome Targets and Regulatory Functions of N6-Methyladenosine (m6A) Writers and Erasers. Evol Bioinform Online 2019;15:1176934319871290. google scholar
  • 47- Kierzek E, Kierzek R. The thermodynamic stability of RNA duplexes and hairpins containing N6-alkyladenosines and 2-methylthio-N6-alkyladenosines. Nucleic Acids Res 2003;31(15):4472-80. google scholar
  • 48- Kennedy EM, Bogerd HP, Kornepati AVR, Kang D, Ghoshal D, Marshall JB, et al. posttranscriptional m6A editing of HIV-1 mRNAs enhances viral gene expression. Cell Host Microbe 2017;22(6):830. google scholar
  • 49- Jenjaroenpun P, Wongsurawat T, Wadley TD, Wassenaar TM, Liu J, Dai Q, et al. Decoding the epitranscriptional landscape from native RNA sequences. Nucleic Acids Res 2021;49(2):e7. google scholar

m6A İLE İLİŞKİLİ VARYANTLARIN SIKLIĞI, ÖRTÜŞTÜĞÜ G-KUADRUPLEKS YAPISININ TERMODİNAMİK KARARLILIĞI İLE DEĞİŞEBİLİR

Year 2023, Volume: 6 Issue: 3, 219 - 228, 24.10.2023

Çağrı Güleç

https://doi.org/10.26650/JARHS2023-1349345

Abstract

Amaç: M6A (N6-metiladenozin) gibi post-transtranskripsiyonel modifikasyonlar ve G-kuadrupleks (G4) gibi ikincil yapılar, RNA işlenmesinde önemli rol oynayan oluşumlardır. Bu iki oluşumun birlikteliğinin de işlevsel sonuçları vardır. M6A oluşumunun DRACH motifi üzerinde enzimatik olarak meydana geldiği, genetik varyantların yeni DRACH motifi oluşturabildiği veya var olan bir DRACH motifini ortadan kaldırabildiği dikkate alındığında, bu tür varyantların, mRNA üzerinde m6A-G4 örtüşme durumunu değiştirerek gen ürün düzeyini etkileyebileceğini, bunun da nesiller boyunca ilgili varyantın alel sıklığını değiştireceğini varsayabiliriz. Bu hipotezi test etmek için seçilmiş hastalık ilişkili genlerdeki nadir ve sık varyantlar DRACH-G4 örtüşmesi yönünden incelendi.
Gereç ve Yöntemler: Genomik diziler ve varyant bilgileri sırasıyla GRCh37/ hg19 ve Biomart-Ensembl veritabanlarından çekildi. Deneysel olarak saptanmış G4 dizileri iki farklı çalışmadan elde edildi.
Bulgular: Yeni bir DRACH motifi oluşumuna yol açan yaygın varyantlar, G4 yapısı içinde yüksek bulundu. Aynı özelliğe sahip nadir varyantlar ise G4 yapısı dışında yüksek bulunurken, pre-mRNA üzerinde eşit dağılım göstermedikleri belirlendi. Yeni bir DRACH motifi oluşumuna yol açan nadir varyantların eşit olmayan dağılımı, örtüştüğü G4 yapısının termodinamik kararlılığı üzerindeki etkisi ile ilişkili bulundu.
Sonuç: Beklenenden sık gözlenen DRACH-G4 örtüşmesi, m6A modifikasyonunun G4 ile örtüştüğü durumların evrimsel bir avantaj sağlıyor olabileceğini düşündürmektedir. Nadir varyantlara bağlı ortaya çıkan DRACH-G4 örtüşmelerinin pre-mRNA’da eşit dağılım göstermemesi ise, m6A’nın G4 termodinamik kararlılığını değiştirmesi ve bu değişikliğin pre-mRNA’nın 5’ kısmına göre 3’ kısmında daha fazla tolere ediliyor olmasına bağlı görünmektedir. Sonuç olarak, DRACH motifi oluşturan varyantların seçilim baskısı ve bunun sonucunda biçimlenen alel sıklığı, bu varyantın pre-mRNA üzerindeki konumuna ve örtüştüğü G4 oluşumunun kararlılığı üzerindeki etkisine göre değişiklik göstermektedir.

Keywords

RNA modifikasyonu N6-metiladenozin G-kuadrupleks alel sıklığı

References

  • 1- Motorin Y, Helm M. RNA nucleotide methylation. Wiley Interdiscip Rev RNA 2011;2(5):611-31. google scholar
  • 2- Machnicka MA, Milanowska K, Oglou OO, Purta E, Kurkowska M, Olchowik A, et al. MODOMICS: a database of RNA modification pathways--2013 update. Nucleic Acids Res 2013;41(Database issue):D262-7. google scholar
  • 3- Desrosiers R, Friderici K, Rottman F. Identification of methylated nucleosides in messenger RNA from Novikoff hepatoma cells. Proc Natl Acad Sci U S A 1974;71(10):3971-5. google scholar
  • 4- Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S, et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature 2012;485(7397):201-6. google scholar
  • 5- Meyer KD, Saletore Y, Zumbo P, Elemento O, Mason CE, Jaffrey SR. Comprehensive analysis of mRNA methylation reveals enrichment in 30 UTRs and near stop codons. Cell 2012;149(7); 1635-46. google scholar
  • 6- Roundtree IA, Evans ME, Pan T, He C. Dynamic RNA modifications in gene expression regulation. Cell 2017;169(7):1187-200. google scholar
  • 7- Zhao BS, Roundtree IA, He C. Post-transcriptional gene regulation by mRNA modifications. Nat Rev Mol Cell Biol 2017;18(1):31-42. google scholar
  • 8- Shi H, Wang X, Lu Z, Zhao BS, Ma H, Hsu PJ, et al. YTHDF3 facilitates translation and decay of N6-methyladenosine-modified RNA. Cell Res 2017;27(3):315-28. google scholar
  • 9- Roignant JY, Soller M. m6A in mRNA: an ancient mechanism for fine-tuning gene expression. Trends Genet 2017;33(6):380-90. google scholar
  • 10- Gilbert WV, Bell TA, Schaening C. Messenger RNA modifications: form, distribution, and function. Science 2016;352(6292):1408-12. google scholar
  • 11- Bochman ML, Paeschke K, Zakian VA. DNA secondary structures: stability and function of G-quadruplex structures. Nat Rev Genet 2012;13(11):770-80. google scholar
  • 12- Rachwal PA, Brown T, Fox KR. Effect of G-tract length on the topology and stability of intramolecular DNA quadruplexes. Biochemistry 2007;46(11):3036-44. google scholar
  • 13- Rachwal PA, Fox KR. Quadruplex melting. Methods 2007;43(4):291-301. google scholar
  • 14- Rachwal PA, Brown T, Fox KR. Sequence effects of single base loops in intramolecular quadruplex DNA. FEBS Lett 2007;581(8):1657-60. google scholar
  • 15- Mukundan VT, Phan AT. Bulges in G-quadruplexes: broadening the definition of G-quadruplex-forming sequences. J Am Chem Soc 2013;135(13):5017-28. google scholar
  • 16- Lam EY, Beraldi D, Tannahill D, Balasubramanian S. G-quadruplex structures are stable and detectable in human genomic DNA. Nat Commun 2013;4:1796. google scholar
  • 17- Bugaut A, Murat P, Balasubramanian S. An RNA hairpin to G-quadruplex conformational transition. J Am Chem Soc 2012;134(49):19953-6. google scholar
  • 18- Huppert JL, Balasubramanian S. G-quadruplexes in promoters throughout the human genome. Nucleic Acids Res 2007;35(2):406-13. google scholar
  • 19- Huppert JL. Hunting G-quadruplexes. Biochimie 2008;90(8):1140-8. google scholar
  • 20- Kumari S, Bugaut A, Huppert JL, Balasubramanian S. An RNA G-quadruplex in the 5’ UTR of the NRAS proto-oncogene modulates translation. Nat Chem Biol 2007;3(4):218-21. google scholar
  • 21- Beaudoin JD, Perreault JP. 5’-UTR G-quadruplex structures acting as translational repressors. Nucleic Acids Res 2010;38(20):7022-36. google scholar
  • 22- Huppert JL, Bugaut A, Kumari S, Balasubramanian S. G-quadruplexes: the beginning and end of UTRs. Nucleic Acids Res 2008;36(19):6260-8. google scholar
  • 23- Thandapani P, Song J, Gandin V, Cai Y, Rouleau SG, Garant JM, et al. Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes. Elife 2015;4:e06234. google scholar
  • 24- Brazda V, Haronı'kova L, Liao JC, Fojta M. DNA and RNA quadruplex-binding proteins. Int J Mol Sci 2014;15(10):17493-517. google scholar
  • 25- Lyons SM, Kharel P, Akiyama Y, Ojha S, Dave D, Tsvetkov V, et al. eIF4G has intrinsic G-quadruplex binding activity that is required for tiRNA function. Nucleic Acids Res 2020;48(11):6223-33. google scholar
  • 26- Niu K, Xiang L, Jin Y, Peng Y, Wu F, Tang W, et al. Identification of LARK as a novel and conserved G-quadruplex binding protein in invertebrates and vertebrates. Nucleic Acids Res 2019;47(14):7306-20. google scholar
  • 27- Williams P, Li L, Dong X, Wang Y. Identification of SLIRP as a G Quadruplex-Binding Protein. J Am Chem Soc 2017;139(36):12426-9. google scholar
  • 28- Serikawa T, Spanos C, von Hacht A, Budisa N, Rappsilber J, Kurreck J. Comprehensive identification of proteins binding to RNA G-quadruplex motifs in the 5’ UTR of tumor-associated mRNAs. Biochimie 2018;144:169-84. google scholar
  • 29- Lyonnais S, Tarres-Sole A, Rubio-Cosials A, Cuppari A, Brito R, Jaumot J, et al. The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein. Sci Rep 2017;7:43992. google scholar
  • 30- Khateb S, Weisman-Shomer P, Hershco-Shani I, Ludwig AL, Fry M. The tetraplex (CGG)n destabilizing proteins hnRNP A2 and CBF-A enhance the in vivo translation of fragile X premutation mRNA. Nucleic Acids Res 2007;35(17):5775-88. google scholar
  • 31- Yang X, Liu QL, Xu W, Zhang YC, Yang Y, Ju LF, et al. m6A promotes R-loop formation to facilitate transcription termination. Cell Res 2019;29(12):1035-8. google scholar
  • 32- Abakir A, Giles TC, Cristini A, Foster JM, Dai N, Starczak M, et al. N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells. Nat Genet 2020;52(1):48-55. google scholar
  • 33- Jara-Espejo M, Fleming AM, Burrows CJ. potential G-quadruplex forming sequences and N6-methyladenosine colocalize at human Pre-mRNA intron splice sites. ACS Chem Biol 2020;15(6):1292-130. google scholar
  • 34- Fleming AM, Nguyen NLB, Burrows CJ. colocalization of m6A and G-Quadruplex-Forming sequences in Viral RNA (HIV, Zika, hepatitis B, and SV40) suggests topological control of adenosine N6-methylation. ACS Cent Sci 2019;5(2):218-28. google scholar
  • 35- Kwok CK, Marsico G, Sahakyan AB, Chambers VS, Balasubramanian S. rG4-seq reveals widespread formation of G-quadruplex structures in the human transcriptome. Nat Methods 2016;13(10):841-4. google scholar
  • 36- Hui WWI, Simeone A, Zyner KG, Tannahill D, Balasubramanian S. Single-cell mapping of DNA G-quadruplex structures in human cancer cells. Sci Rep 2021;11(1):23641. google scholar
  • 37- Csepany T, Lin A, Baldick CJ Jr, Beemon K. Sequence specificity of mRNA N6-adenosine methyltransferase. J Biol Chem 1990;265(33):20117-22. google scholar
  • 38- Bushkin GG, Pincus D, Morgan JT, Richardson K, Lewis C, Chan SH, et al. m6A modification of a 3’ UTR site reduces RME1 mRNA levels to promote meiosis. Nat Commun 2019;10(1):3414. google scholar
  • 39- Batista PJ, Molinie B, Wang J, Qu K, Zhang J, Li L, et al. m(6)A RNA modification controls cell fate transition in mammalian embryonic stem cells. Cell Stem Cell 2014;15(6):707-19. google scholar
  • 40- Rouleau S, Glouzon JS, Brumwell A, Bisaillon M, Perreault JP. 3’ UTR G-quadruplexes regulate miRNA binding. RNA 2017;23(8):1172-9. google scholar
  • 41- Jodoin R, Carrier JC, Rivard N, Bisaillon M, Perreault JP. G-quadruplex located in the 5’UTR of the BAG-1 mRNA affects both its cap-dependent and cap-independent translation through global secondary structure maintenance. Nucleic Acids Res 2019;47(19):10247-66. google scholar
  • 42- Song J, Perreault JP, Topisirovic I, Richard S. RNA G-quadruplexes and their potential regulatory roles in translation. Translation (Austin) 2016;4(2):e1244031. google scholar
  • 43- von Hacht A, Seifert O, Menger M, Schütze T, Arora A, Konthur Z, et al. Identification and characterization of RNA guanine-quadruplex binding proteins. Nucleic Acids Res 2014;42(10):6630-44. google scholar
  • 44- Roundtree IA, He C. Nuclear m(6)A Reader YTHDC1 Regulates mRNA Splicing. Trends Genet 2016;32(6):320-1. google scholar
  • 45- Xue Y, Liu JQ, Zheng KW, Kan ZY, Hao YH, Tan Z. Kinetic and thermodynamic control of G-quadruplex folding. Angew Chem Int Ed Engl 2011;50(35):8046-50. google scholar
  • 46- Song Y, Xu Q, Wei Z, Zhen D, Su J, Chen K, Meng J. Predict Epitranscriptome Targets and Regulatory Functions of N6-Methyladenosine (m6A) Writers and Erasers. Evol Bioinform Online 2019;15:1176934319871290. google scholar
  • 47- Kierzek E, Kierzek R. The thermodynamic stability of RNA duplexes and hairpins containing N6-alkyladenosines and 2-methylthio-N6-alkyladenosines. Nucleic Acids Res 2003;31(15):4472-80. google scholar
  • 48- Kennedy EM, Bogerd HP, Kornepati AVR, Kang D, Ghoshal D, Marshall JB, et al. posttranscriptional m6A editing of HIV-1 mRNAs enhances viral gene expression. Cell Host Microbe 2017;22(6):830. google scholar
  • 49- Jenjaroenpun P, Wongsurawat T, Wadley TD, Wassenaar TM, Liu J, Dai Q, et al. Decoding the epitranscriptional landscape from native RNA sequences. Nucleic Acids Res 2021;49(2):e7. google scholar
There are 49 citations in total.

Details

Primary Language English
Subjects Clinical Sciences (Other)
Journal Section Research Articles
Authors

Çağrı Güleç 0000-0002-1256-9574

Publication Date October 24, 2023
Submission Date August 24, 2023
Published in Issue Year 2023 Volume: 6 Issue: 3

Cite

MLA Güleç, Çağrı. “THE FREQUENCY AND FITNESS OF m6A-ASSOCIATED VARIANTS COULD BE MODULATED BY THE THERMODYNAMIC STABILITY OF AN OVERLAPPING G-QUADRUPLEX”. Sağlık Bilimlerinde İleri Araştırmalar Dergisi, vol. 6, no. 3, 2023, pp. 219-28, doi:10.26650/JARHS2023-1349345.
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