Infection Medicine

New paper by Michlewski lab published in Nature Communications

Dr Gracjan Michlewski, Principal Investigator at Infection Medicine, published a new paper in Nature Communications.

Dr Gracjan Michlewski has published a paper in Nature Communications - "Loss of 5-methylcytosine alters the biogenesis of Vault-derived small RNAs to coordinate epidermal differentiation".

Summary of findings:

Summary of VTRNA1.1 processing into svRNA4. A) Expression of both NSUN2 and SRSF2 (e.g. in progenitor cells) result in high levels of VTRNA1.1 methylation (CH3 – m5C) and high levels of svRNA4 and repressed differentiation. B) No NSUN2 in the presence of SRSF2 suppresses formation of svRNA4 and allows differentiation. C) Lack of expression of both NSUN2 and SRSF2 release VTRNA1.1 from SRSF2 binding and increases the levels of svRNA4.
Summary of VTRNA1.1 processing into svRNA4. A) Expression of both NSUN2 and SRSF2 (e.g. in progenitor cells) result in high levels of VTRNA1.1 methylation (CH3 – m5C) and high levels of svRNA4 and repressed differentiation. B) No NSUN2 in the presence of SRSF2 suppresses formation of svRNA4 and allows differentiation. C) Lack of expression of both NSUN2 and SRSF2 release VTRNA1.1 from SRSF2 binding and increases the levels of svRNA4.

The presence and absence of RNA modifications regulates RNA metabolism which contributes to cellular and organismal development and function. Working in collaboration with Professor Michaela Frye (University of Cambridge and German Cancer Research Centre), we decipher the consequences of 5-methylcytosine (m5C) deposition by NOP2/Sun RNA Methyltransferase 2 (NSUN2) into the abundant non-coding vault RNA VTRNA1.1. We identify the serine/arginine rich splicing factor 2 (SRSF2) as a novel VTRNA1.1-binding protein. Finally, we demonstrate a functional relationship between SRSF2, m5C and VTRNA1.1 processing into small vault RNA (svRNA) in regulating the epidermal differentiation programme.

Significance:

This study is important as m5C modification in RNA is very common. However, it is largely unknown what are the functional consequences in terms of molecular mechanisms as well as cellular and organismal functions of this RNA modification.