NSUN6, an RNA methyltransferase of 5-mC controls glioblastoma response to temozolomide (TMZ) via NELFB and RPS6KB2 interaction. Issue 10 (2nd December 2021)

• Record Type: Journal Article
• Authors: Awah, Chidiebere U; Winter, Jan; Mazdoom, Claudiane M; Ogunwobi, Olorunseun O.
• Is Part Of: Cancer biology & therapy. Volume 22:Issue 10/12(2021)
• Page Start: 587
• Page End: 597
• Publication Date: 2021-12-02
• Subjects: NSUN6 -- 5mC -- RNA methyltransferase -- CRISPR Cas9a -- epitranscriptomics -- glioblastoma -- temozolomide -- pre-initiation complex -- general transcription factor complexes -- transcriptional pausing; 616.99406
• DOI: 10.1080/15384047.2021.1990631
• Languages: English
• ISSNs: 1538-4047

Abstract

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.