Emerging role of N4-acetylcytidine modification of RNA in gene regulation and cellular functions
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MINI REVIEW ARTICLE
Emerging role of N4‑acetylcytidine modification of RNA in gene regulation and cellular functions R. Karthiya1 · S. Mohammed Wasil1 · Piyush Khandelia1 Received: 13 July 2020 / Accepted: 29 October 2020 © Springer Nature B.V. 2020
Abstract Post-transcriptional chemical modification of RNA is rapidly emerging as a key player in regulating gene expression and has propelled the development of ‘epitranscriptomics’ or ‘RNA epigenetics’ as a frontier area of research. Several RNA modifications are known to decorate RNAs and impact its structure and function. One such recently discovered modification is acetylation of RNA i.e. N4-acetylcytidine (ac4C) chemical modification. N4-acetylcytidine is an ancient and evolutionarily conserved modification, which maps to a wide spectrum of RNAs from archaea bacteria to humans. This modification results in a variety of functional outcomes which impact normal development and disease. In this review, we summarize the recent progress, emerging methods, biological implications and the future challenges for ac4C modification. Keywords Gene regulation · RNA modification · RNA acetylation · N4-acetylcytidine · ac4C
Introduction As opposed to the epigenome, which consists of a few well studied modified bases, various classes of RNA are decorated by > 140 different chemical modifications, which together constitute the RNA epigenome or epitranscriptome [1–3]. Discovery of epitranscriptome has opened up novel avenues for gene regulation by expanding the regulatory functions of RNA via influencing various aspects of RNA metabolism like stability, structure, translation, localization, splicing to name a few [1–3]. All classes of cellular RNAs, be it coding RNAs like messenger RNAs (mRNAs) or non-coding RNAs like transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and circular RNAs (circRNAs) harbor epitranscriptomic chemical modifications [1–3]. Some of the common internal modifications which are suggested to adorn mRNAs and lncRNAs are N6-methyladenosine (m6A), inosine, pseudouridine, 5-methycytidine, N6,2′-O-dimethyladenosine, 2′-O-methyl * Piyush Khandelia [email protected]‑pilani.ac.in; [email protected] 1
Department of Biological Sciences, Birla Institute of Technology and Science, Pilani ‑ Hyderabad Campus, Jawahar Nagar, Kapra Mandal, Medchal District, Hyderabad, Telangana 500078, India
and N1-methyladenosine (m1A) [1–3]. Till date, a majority of these chemical modifications are predicted to be static and irreversible, with the exception on m6A and m1A which are dynamic and reversible in nature with m6A being the prime driver of the field of epitranscriptomics [2–5]. However, the possibility of many of these static modifications to be reversible cannot be ruled out. Their static nature is predicted primarily due to the lack of information on the corresponding ‘eraser’ protein which removes the modification mark, however the discovery of such ‘erasers’ in near future, can very well change the
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