Sense-overlapping lncRNA as a decoy of translational repressor protein for dimorphic gene expression

PLoS Genet. 2021 Jul 28;17(7):e1009683. doi: 10.1371/journal.pgen.1009683. eCollection 2021 Jul.

Abstract

Long noncoding RNAs (lncRNAs) are vastly transcribed and extensively studied but lncRNAs overlapping with the sense orientation of mRNA have been poorly studied. We analyzed the lncRNA DAPALR overlapping with the 5´ UTR of the Doublesex1 (Dsx1), the male determining gene in Daphnia magna. By affinity purification, we identified an RNA binding protein, Shep as a DAPALR binding protein. Shep also binds to Dsx1 5´ UTR by recognizing the overlapping sequence and suppresses translation of the mRNA. In vitro and in vivo analyses indicated that DAPALR increased Dsx1 translation efficiency by sequestration of Shep. This regulation was impaired when the Shep binding site in DAPALR was deleted. These results suggest that Shep suppresses the unintentional translation of Dsx1 by setting a threshold; and when the sense lncRNA DAPALR is expressed, DAPALR cancels the suppression caused by Shep. This mechanism may be important to show dimorphic gene expressions such as sex determination and it may account for the binary expression in various developmental processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions / genetics
  • Animals
  • Binding Sites / genetics
  • DNA-Binding Proteins / genetics
  • Daphnia / genetics
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Gene Expression / genetics
  • Gene Expression Regulation / genetics*
  • Gene Expression Regulation / physiology
  • Male
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Sex Determination Processes / genetics*

Substances

  • 5' Untranslated Regions
  • DNA-Binding Proteins
  • DSX protein, Drosophila
  • Drosophila Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • RNA-Binding Proteins
  • Shep protein, Drosophila

Grants and funding

This work was supported by 17H05610, 20H04853 to S.A., 20H04923, 19H05423, 18H04884 and 17H05602 to K.Y. and 18H04619, 17K19236 and 17H01880 to H.W. from Japan Science Promotion Society (JSPS), Japan (https://www.jsps.go.jp/english/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.