Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)
Published: Feb. 4, 2025
Language: Английский
Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)
Published: Sept. 22, 2022
RNA modifications have become hot topics recently. By influencing processes, including generation, transportation, function, and metabolization, they act as critical regulators of cell biology. The immune abnormality in human diseases is also a research focus progressing rapidly these years. Studies demonstrated that participate the multiple biological processes cells, development, differentiation, activation, migration, polarization, thereby modulating responses are involved some related diseases. In this review, we present existing knowledge functions underlying mechanisms modifications, N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A), N7-methylguanosine (m7G), N4-acetylcytosine (ac4C), pseudouridine (Ψ), uridylation, adenosine-to-inosine (A-to-I) editing, summarize their roles Via regulating can pathogenesis diseases, such cancers, infection, inflammatory autoimmune We further highlight challenges future directions based on knowledge. All all, review will provide helpful well novel ideas for researchers area.
Language: Английский
Citations
210
Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(10), P. 714 - 731
Published: June 27, 2023
Language: Английский
Citations
138
Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 25(2), P. 104 - 122
Published: Sept. 15, 2023
Language: Английский
Citations
132
Trends in Pharmacological Sciences, Journal Year: 2022, Volume and Issue: 43(6), P. 522 - 535
Published: April 21, 2022
Pseudouridine (Ψ) is the most common post-transcriptional RNA modification that dynamically deposited throughout transcriptome.RNA pseudouridylation can influence various cellular processes, such as translation and response to environmental stress, becomes dysregulated in disease.Mutations Ψ synthases lead aberrant of their targets contribute cancer progression genetic disease.The level excreted expression profile machinery may have diagnostic prognostic value biomarkers for cancer.The dynamic epitranscriptome a potential target therapeutic development. abundant widespread multiple species. impacts aspects biology, conferring distinct structural functional properties molecules it decorates. However, contributes variety human diseases, including disorders. Dysregulation arise from mutations abnormal machinery, impacting protein other processes. With advancing understanding roles health disease, efforts are now invested developing approaches targeting Ψ. Emerging reports indicate its installation could be pharmacological development serve diseases. The presence modified nucleosides (see Glossary) was discovered 1950s [1.Lane B.G. Historical perspectives on nucleoside modifications.in: Grosjean H. Benne R. Modification Editing RNA. ASM Press, 1998: 1-20Crossref Google Scholar]. To date, over 170 different modifications been identified with wide chemical diversities [2.Boccaletto P. et al.MODOMICS: database pathways. 2021 update.Nucleic Acids Res. 2022; 50: D231-D235Crossref PubMed Scopus (22) Unlike genomic DNA, which tends limited variation moieties, range appears strategy used by nature give much greater diversity structures functions In recent years, emerging sequencing technologies, combining accurate labeling strategies next-generation sequencing, fueled discoveries field [3.Helm M. Motorin Y. Detecting epitranscriptome: predict validate.Nat. Rev. Genet. 2017; 18: 275-291Crossref (325) success deciphering modifications, N6-methyladenosine (m6A) [4.Zaccara S. al.Reading, writing erasing mRNA methylation.Nat. Mol. Cell Biol. 2019; 20: 608-624Crossref (565) Scholar], modulating landscapes therapy [5.Yankova E. al.Small-molecule inhibition METTL3 against myeloid leukaemia.Nature. 2021; 593: 597-601Crossref (126) Scholar, 6.Cully Chemical inhibitors make epigenetic mark.Nat. Drug Discov. 892-894Crossref (28) 7.Cui Q. al.m(6)A Methylation regulates self-renewal tumorigenesis glioblastoma stem cells.Cell Rep. 2622-2634Abstract Full Text PDF (660) has sparked interest many study accelerating epitranscriptomics. (Ψ), known 'fifth nucleotide' RNA, first 1951 Scholar,8.Cohn W.E. Volkin Nucleoside-5-phosphates ribonucleic acid.Nature. 1951; 167: 483-484Crossref (124) It species [9.Li X. al.Pseudouridine: fifth nucleotide renewed interests.Curr. Opin. Chem. 2016; 33: 108-116Crossref (79) Scholar,10.Ge J. Yu Y.T. pseudouridylation: new insights into an old modification.Trends Biochem. Sci. 2013; 38: 210-218Abstract (159) C–C glycosidic isomer uridine (U) incorporates C5 atom nucleobase bond extra hydrogen donor non-Watson–Crick edge host stability [11.Kierzek al.The contribution pseudouridine stabilities structure RNAs.Nucleic 2014; 42: 3492-3501Crossref (121) importance processes prompted investigators diseases so novel therapeutics processing developed. present review we discuss basic contributions disorders, better understand important consider how installed affects molecules. Dyskerin (DKC1) stand-alone (PUSs) catalyze RNA-dependent RNA-independent mechanisms, respectively (Box 1) [12.Borchardt E.K. al.Regulation function cells.Annu. 2020; 54: 309-336Crossref (23) 13.Penzo Montanaro L. Turning uridines around: role rRNA ribosome biogenesis ribosomal function.Biomolecules. 2018; 8: 38Crossref (38) 14.Rintala-Dempsey A.C. Kothe U. Eukaryotic – modifying enzymes regulators gene expression?.RNA 14: 1185-1196Crossref (73) complex DKC1, small-nucleolar RNAs (snoRNAs) guide pseudouridylation, whereas small Cajal body-specific (scaRNAs) nuclear (snRNA) pseudouridylation. PUS decorate substrates, tRNAs, mRNAs, others. When installed, confers RNAs, affecting translation, biogenesis, processes.Box 1The mechanisms pseudouridylationPseudouridylation catalyzed or mechanism. mechanism, carried out single (Figure IA). Human share core fold, conserved active-site cleft, catalytically essential aspartate residue [14.Rintala-Dempsey Individual proteins both unique overlapping substrates diverse species, pre-mRNAs, Moreover, localization nucleus, cytoplasm, mitochondria, well relocalization upon stimuli, substrate pool available [21.Schwartz al.Transcriptome-wide mapping reveals dynamic-regulated ncRNA mRNA.Cell. 159: 148-162Abstract (552) Scholar].The mechanism relies RNA–protein complexes box H/ACA ribonucleoproteins, consist noncoding four proteins, GAR1, NOP10, NHP2 IB) [100.Hamma T. Ferre-D'Amare A.R. ribonucleoprotein complex: interplay modification.J. 2010; 285: 805-809Abstract (65) Box adopt hairpin–hinge–hairpin–tail structure, hinge tail part work sequence-specific pairing hairpin forms large internal loop referred pocket [56.McMahon al.Small big implications: snoRNA disease.Wiley Interdiscip. 2015; 6: 173-189Crossref (78) DKC1 interacts installs within pocket. found nucleolus bodies thus classified snoRNAs scaRNAs, respectively. Whereas rRNAs, scaRNAs required snRNA Both pseudouridylated at functionally regions, while lack affect functionality [13.Penzo Scholar,28.Deryusheva Gall J.G. Orchestrated positioning branch point recognition region U2 snRNA.RNA. 24: 30-42Crossref (11) Scholar,29.Bohnsack M.T. Sloan K.E. Modifications spliceosome assembly function.Biol. 399: 1265-1276Crossref (52) Apart catalyzing U isomerization Ψ, also telomerase component (TERC), leading stabilization [41.Nagpal N. Agarwal Telomerase processing: Implications disease.Stem Cells. 1532-1543Crossref (12) Pseudouridylation regulation critical steering programs disease. reflected distribution, influencing key modalities involved translation: rRNA, tRNA, (Table 1). accounts about 1.4% all bases rRNAs shown modulate conformational dynamics Scholar,15.Jiang al.Modulation changes helix 69 mutants modifications.Biophys. 200-201: 48-55Crossref (5) clustered regions binding sites tRNAs mRNAs [10.Ge increases affinity tRNA A P sites, defects decrease ribosome–ligand interactions translational fidelity [16.Jack K. al.rRNA ligand yeast cells.Mol. Cell. 2011; 44: 660-666Abstract (184) nearly TΨC stem–loop Ψ55, less frequently positions, Ψ13 Ψ39, stabilize specific [17.Gray Charette Michael W. RNA: what, where, how, why.IUBMB Life. 2000; 49: 341-351Crossref (376) Scholar,18.Motorin Helm nucleotides.Biochemistry. 4934-4944Crossref (300) influences altering tRNA-derived fragments (tRFs); Guzzi al. one type tRF termed mTOGs inhibited cap-dependent only when decorated Ψ8 PUS7 [19.Guzzi al.Pseudouridylation steers control cells.Cell. 173: 1204-1216. e26Abstract (175) worth noting not detected must tRFs Scholar].Table biologyProcessRNA classFunctionStudied modelDetection methodRefsTranslationrRNAAffects fidelityVariousHPLC[16.Jack Scholar]TranslationrRNAAlters decodingVariousSCARLET[37.McMahon al.A nucleolar mediates tumor suppression downstream oncogenic RAS.elife. 8e48847Crossref (54) Scholar]TranslationrRNAModulates dynamicsThermodynamic analysisUsed chemically synthesized RNA[15.Jiang Scholar]TranslationtRNARegulates functionhESCsSCARLET CMC-based RT-qPCR[19.Guzzi Scholar]TranslationtRNAModulates codon-biased translationGSCsPseudo-seq DM-Ψ-seq[38.Cui al.Targeting suppresses tumorigenesis.Nat. Cancer. 2: 932-949Crossref (9) Scholar]TranslationmRNASuppresses termination expands codeS. cerevisiaeUsed RNA[24.Karijolich Converting nonsense codons sense targeted pseudouridylation.Nature. 474: 395Crossref (209) Scholar]TranslationmRNAAccommodates noncanonical base pairsCrystallographic RNA[25.Fernandez I.S. al.Unusual during decoding stop codon ribosome.Nature. 500: 107-110Crossref (108) Scholar]TranslationmRNAAffects kinetic parameters ribosomesVariousUsed RNA[26.Eyler D.E. al.Pseudouridinylation coding sequences alters translation.Proc. Natl. Acad. A. 116: 23068-23074Crossref (50) Scholar]SplicingsnRNAModulates pre-mRNA splicingS. cerevisiaeCMC-based primer extension TLC[32.Basak Query C.C. filamentous growth program yeast.Cell 966-973Abstract (46) Scholar,33.Wu G. al.U2 inducibly Pus7p snR81 RNP.EMBO 30: 79-89Crossref (109) Scholar]Splicingpre-mRNAModulates splicingX. laevisUsed vitro RNA[34.Chen C. flexible backbone polypyrimidine tract U2AF65 splicing vivo.Mol. 4108-4119Crossref (30) alternative splicingHepG2 cell linePseudo-seq[35.Martinez N.M. al.Pseudouridine modify co-transcriptionally processing.Mol. 82: 645-659 e9Abstract Scholar]RNA stabilityVariousStabilizes duplexesThermodynamic RNA[11.Kierzek Scholar]Protein–RNA interactionVariousModulates bindingVariousUsed RNA[97.Vaidyanathan P.P. N(6)-methyladenosine weaken PUF protein/RNA interactions.RNA. 23: 611-618Crossref (32) 98.Delorimier inhibits muscleblind-like 1 (MBNL1) CCUG repeats minimally structured through reduced flexibility.J. 292: 4350-4357Abstract (26) 99.Levi O. Arava Y.S. Pseudouridine-mediated methionine aminoacyl synthetase.Nucleic 432-443Crossref (10) Scholar]Response environmentVariousModulates heat shock, nutrient deprivation, othersVariousVarious[20.Carlile T.M. profiling regulated cells.Nature. 515: 143-146Crossref (560) 21.Schwartz 22.Li al.Chemical pulldown mammalian transcriptome.Nat. 11: 592-597Crossref (292) Scholar,27.Song D. al.HSP90-dependent overexpression facilitates metastasis colorectal cells regulating LASP1 abundance.J. Exp. Clin. Cancer 40: 170Crossref (2) Scholar,31.Wu TOR signaling pathway starvation-induced 22: 1146-1152Crossref Scholar]HPLC, high-performance liquid chromatography; SCARLET, site-specific cleavage radioactive followed ligation-assisted extraction thin-layer tRF, fragment; hESCs, embryonic cells; RT-qPCR, reverse transcription-quantitative polymerase chain reaction; CMC, N-cyclohexyl-N′-β-(4-methylmorpholinium) ethylcarbodiimide p-tosylate; GSCs, Pseudo-seq DM-Ψ-seq, high-throughput detection methods; cerevisiae, Saccharomyces cerevisiae; TLC, laevis, Xenopus laevis. Open table tab HPLC, Until recently, technically challenging due lower abundance transcripts compared classes limiting our biology. methods, thousands mRNA, revealing ubiquitous distribution tendency enriched sequence (CDS) 3′-untranslated (3′UTR) [20.Carlile 23.Karijolich pseudouridylation.Nat. 16: 581-585Crossref Although context-dependent beginning understood, steps mostly studied translation. Karijolich demonstrated Ψ-modified (ΨAA, ΨAG, ΨGA) suppressed yeast, readthrough premature (PTC)-bearing [24.Karijolich unusual base-pairing geometry further confirmed crystallographic analysis [25.Fernandez These data suggest regulate even expand code, ΨAA ΨAG encode serine threonine ΨGA tyrosine phenylalanine. Eyler ribosomes were affected codons, associated more frequent amino acid substitutions non-pseudouridylated [26.Eyler Importantly, authors argued effects context-dependent, indicating complexity Ψ-dependent generalized mechanisms. becoming evident remodeled stimuli stress. Transcriptome-wide revealed 265 induced cerevisiae attributed relocation nucleus cytoplasm study, shock H2O2 treatment, contributed stimuli-specific landscape [22.Li Furthermore, Song implicated heat-shock HSP90 partner PUS7, suggesting link between stress [27.Song Biochemical assays stabilized prevented proteasomal degradation. provide layer regulation, dependent changing conditions. consequences inducible individual remain largely unknown factors interact Ψ-decorated All five spliceosomal snRNAs extensively tightly orderly process, correct [28.Deryusheva 29.Bohnsack 30.Morais al.Spliceosomal epitranscriptomics.Front. 12652129Crossref findings U6 states global scale cues [31.Wu Scholar,32.Basak p
Language: Английский
Citations
91
Nature Chemical Biology, Journal Year: 2023, Volume and Issue: 19(10), P. 1185 - 1195
Published: March 30, 2023
Language: Английский
Citations
83
Journal of Hematology & Oncology, Journal Year: 2023, Volume and Issue: 16(1)
Published: June 22, 2023
Abstract Small RNAs (also referred to as small noncoding RNAs, sncRNA) are defined polymeric ribonucleic acid molecules that less than 200 nucleotides in length and serve a variety of essential functions within cells. RNA species include microRNA (miRNA), PIWI-interacting (piRNA), interfering (siRNA), tRNA-derived (tsRNA), etc. Current evidence suggest can also have diverse modifications their nucleotide composition affect stability well capacity for nuclear export, these relevant drive molecular signaling processes biogenesis, cell proliferation differentiation. In this review, we highlight the characteristics cellular modifications, current techniques reliable detection. We discuss how may be clinical applications diagnosis treatment human health conditions such cancer.
Language: Английский
Citations
53
Annual Review of Immunology, Journal Year: 2023, Volume and Issue: 41(1), P. 73 - 98
Published: April 26, 2023
Characterization of RNA modifications has identified their distribution features and molecular functions. Dynamic changes in modification on various forms are essential for the development function immune system. In this review, we discuss value innovative profiling technologies to uncover these diverse, dynamic cells within healthy diseased contexts. Further, explore our current understanding mechanisms whereby aberrant modulate milieu tumor microenvironment point out outstanding research questions.
Language: Английский
Citations
46
Molecular Cell, Journal Year: 2023, Volume and Issue: 83(22), P. 3953 - 3971
Published: Oct. 5, 2023
tRNA function is based on unique structures that enable mRNA decoding using anticodon trinucleotides. These interact with specific aminoacyl-tRNA synthetases and ribosomes 3D shape sequence signatures. Beyond translation, tRNAs serve as versatile signaling molecules interacting other RNAs proteins. Through evolutionary processes, fragmentation emerges not merely random degradation but an act of recreation, generating shorter called tRNA-derived small (tsRNAs). tsRNAs exploit their linear sequences newly arranged for unexpected biological functions, epitomizing the "renovatio" (from Latin, meaning renewal, renovation, rebirth). Emerging methods to uncover full tRNA/tsRNA modifications, combined techniques study RNA integrate AI-powered predictions, will comprehensive investigations products new interaction potentials in relation functions. We anticipate these directions herald a era understanding complexity advancing pharmaceutical engineering.
Language: Английский
Citations
45
Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)
Published: March 27, 2024
Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells. Relevant studies have been constantly making inroads in our understanding pathophysiology, inspiring development therapeutics. As a crucial component epigenetics at post-transcription level, RNA modification significantly determines fates, further affecting various biological processes cellular phenotypes. To be noted, immunometabolism defines the metabolic alterations occur on immune cells different stages immunological contexts. In this review, we characterize distribution features, modifying mechanisms functions 8 modifications, including N6-methyladenosine (m6A), N6,2'-O-dimethyladenosine (m6Am), N1-methyladenosine (m1A), 5-methylcytosine (m5C), N4-acetylcytosine (ac4C), N7-methylguanosine (m7G), Pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing, which are relatively most studied types. Then regulatory roles these diverse health disease contexts comprehensively described, categorized as glucose, lipid, amino acid, mitochondrial metabolism. And highlight regulation modifications immunometabolism, influencing responses. Above all, provide thorough discussion about clinical implications metabolism-targeted therapy immunotherapy, progression modification-targeted agents, its potential RNA-targeted Eventually, give legitimate perspectives for future researches field from methodological requirements, mechanistic insights, to therapeutic applications.
Language: Английский
Citations
36
Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(5), P. 359 - 378
Published: Jan. 5, 2024
Language: Английский
Citations
27