The m6A pathway facilitates sex determination in Drosophila. Academic Article uri icon

Overview

abstract

  • The conserved modification N6-methyladenosine (m6A) modulates mRNA processing and activity. Here, we establish the Drosophila system to study the m6A pathway. We first apply miCLIP to map m6A across embryogenesis, characterize its m6A 'writer' complex, validate its YTH 'readers' CG6422 and YT521-B, and generate mutants in five m6A factors. While m6A factors with additional roles in splicing are lethal, m6A-specific mutants are viable but present certain developmental and behavioural defects. Notably, m6A facilitates the master female determinant Sxl, since multiple m6A components enhance female lethality in Sxl sensitized backgrounds. The m6A pathway regulates Sxl processing directly, since miCLIP data reveal Sxl as a major intronic m6A target, and female-specific Sxl splicing is compromised in multiple m6A pathway mutants. YT521-B is a dominant m6A effector for Sxl regulation, and YT521-B overexpression can induce female-specific Sxl splicing. Overall, our transcriptomic and genetic toolkit reveals in vivo biologic function for the Drosophila m6A pathway.

publication date

  • July 4, 2017

Research

keywords

  • Adenosine
  • Drosophila melanogaster
  • Gene Expression Regulation, Developmental
  • RNA-Binding Proteins
  • Sex Determination Processes

Identity

PubMed Central ID

  • PMC5500889

Scopus Document Identifier

  • 85021701290

Digital Object Identifier (DOI)

  • 10.1038/ncomms15737

PubMed ID

  • 28675155

Additional Document Info

volume

  • 8