NSUN6, an RNA methyltransferase of 5-mC controls glioblastoma response to temozolomide (TMZ) via NELFB and RPS6KB2 interaction. Academic Article uri icon

Overview

abstract

  • Nop2/Sun RNA methyltransferase (NSUN6) is an RNA 5-methyl cytosine (5mC) transferase with little information known of its function in cancer and response to cancer therapy. Here, we show that NSUN6 methylates both large and small RNA in glioblastoma and controls glioblastoma response to temozolomide with or without influence of the MGMT promoter status, with high NSUN6 expression conferring survival benefit to glioblastoma patients and in other cancers. Mechanistically, our results show that NSUN6 controls response to TMZ therapy via 5mC-mediated regulation of NELFB and RPS6BK2. Taken together, we present evidence that show that NSUN6-mediated 5mC deposition regulates transcriptional pause by accumulation of NELFB and the general transcription factor complexes (POLR2A, TBP, TFIIA, and TFIIE) on the preinitiation complex at the TATA binding site to control translation machinery in glioblastoma response to alkylating agents. Our findings open a new frontier into controlling of transcriptional regulation by RNA methyltransferase and 5mC.

publication date

  • October 27, 2021

Research

keywords

  • Brain Neoplasms
  • Glioblastoma
  • Ribosomal Protein S6 Kinases, 70-kDa
  • Temozolomide
  • Transcription Factors

Identity

PubMed Central ID

  • PMC8726740

Scopus Document Identifier

  • 85118922148

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2019.01.033

PubMed ID

  • 34705606

Additional Document Info

volume

  • 22

issue

  • 10-12