Human RNA cap1 methyltransferase CMTr1 cooperates with RNA helicase DHX15 to modify RNAs with highly structured 5ʹ termini

• Published in: Philosophical transactions of the Royal Society of London. Series B. Biological sciences Vol. 373; no. 1762; pp. 1 - 10
• Main Authors: Toczydlowska-Socha, Diana, Zielinska, Magdalena M., Kurkowska, Malgorzata, Astha, Almeida, Catarina F., Stefaniak, Filip, Purta, Elzbieta, Bujnicki, Janusz M.
• Format: Journal Article
• Language: English
• Published: Royal Society 19-12-2018
• ISSN: 0962-8436; 1471-2970

The 5ʹ-cap structure, characteristic for RNA polymerase II-transcribed RNAs, plays important roles in RNA metabolism. In humans, RNA cap formation includes post-transcriptional modification of the first transcribed nucleotide by RNA cap1 methyltransferase (CMTr1). Here, we report that CMTr1 activity is hindered towards RNA substrates with highly structured 5ʹ termini. We found that CMTr1 binds ATP-dependent RNA DHX15 helicase and that this interaction, mediated by the G-patch domain of CMTr1, has an advantageous effect on CMTr1 activity towards highly structured RNA substrates. The effect of DHX15 helicase activity is consistent with the strength of the secondary structure that has to be removed for CMTr1 to access the 5ʹ-terminal residues in a single-stranded conformation. This is, to our knowledge, the first demonstration of the involvement of DHX15 in post-transcriptional RNA modification, and the first example of a molecular process in which DHX15 directly affects the activity of another enzyme. Our findings suggest a new mechanism underlying the regulatory role of DHX15 in the RNA capping process. RNAs with highly structured 5ʹ termini constitute a significant fraction of the human transcriptome. Hence, CMTr1–DHX15 cooperation is likely to be important for the metabolism of RNA polymerase II-transcribed RNAs.
This article is part of the theme issue '5ʹ and 3ʹ modifications controlling RNA degradation'.