Abstract:
:The presence and absence of RNA modifications regulates RNA metabolism by modulating the binding of writer, reader, and eraser proteins. For 5-methylcytosine (m5C) however, it is largely unknown how it recruits or repels RNA-binding proteins. Here, we decipher the consequences of m5C deposition into the abundant non-coding vault RNA VTRNA1.1. Methylation of cytosine 69 in VTRNA1.1 occurs frequently in human cells, is exclusively mediated by NSUN2, and determines the processing of VTRNA1.1 into small-vault RNAs (svRNAs). We identify the serine/arginine rich splicing factor 2 (SRSF2) as a novel VTRNA1.1-binding protein that counteracts VTRNA1.1 processing by binding the non-methylated form with higher affinity. Both NSUN2 and SRSF2 orchestrate the production of distinct svRNAs. Finally, we discover a functional role of svRNAs in regulating the epidermal differentiation programme. Thus, our data reveal a direct role for m5C in the processing of VTRNA1.1 that involves SRSF2 and is crucial for efficient cellular differentiation.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Sajini AA,Choudhury NR,Wagner RE,Bornelöv S,Selmi T,Spanos C,Dietmann S,Rappsilber J,Michlewski G,Frye Mdoi
10.1038/s41467-019-10020-7subject
Has Abstractpub_date
2019-06-11 00:00:00pages
2550issue
1issn
2041-1723pii
10.1038/s41467-019-10020-7journal_volume
10pub_type
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