Loss of 5-methylcytosine alters the biogenesis of vault-derived small RNAs to coordinate epidermal differentiation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31186410.
- Also identified by DOI 10.1038/s41467-019-10020-7 and PMC identifier 6560067.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The presence and absence of RNA modifications regulates RNA metabolism by modulating the binding of writer, reader, and eraser proteins. For 5-methylcytosine (m<sup>5</sup>C) however, it is largely unknown how it recruits or repels RNA-binding proteins. Here, we decipher the consequences of m<sup>5</sup>C 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 m<sup>5</sup>C in the processing of VTRNA1.1 that involves SRSF2 and is crucial for efficient cellular differentiation.
Medical subject headings
- 5-Methylcytosine
- DNA Methylation
- Epidermal Cells
- Methyltransferases
- RNA
- Vault Ribonucleoprotein Particles