Auto- and cross-regulation of the hnRNPs D and DL

RNA. 2018 Mar;24(3):324-331. doi: 10.1261/rna.063420.117. Epub 2017 Dec 20.

Abstract

HnRNP D, better known as AUF1, is an extensively studied protein that controls a variety of cellular pathways. Consequently, its expression has to be tightly regulated to prevent the onset of pathologies. In contrast, the cellular functions and regulation of its ubiquitously expressed paralog hnRNP DL are barely explored. Here, we present an intricate crosstalk between these two proteins. Both hnRNP D and DL are able to control their own expression by alternative splicing of cassette exons in their 3'UTRs. Exon inclusion produces mRNAs degraded by nonsense-mediated decay. Moreover, hnRNP D and DL control the expression of one another by the same mechanism. Thus, we identified two novel ways of how hnRNP D expression is controlled. The tight interconnection of expression control directly links hnRNP DL to hnRNP D-related diseases and emphasizes the importance of a systematic analysis of its cellular functions.

Keywords: NMD; autoregulation; cassette exon; hnRNP; splicing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Alternative Splicing*
  • Exons
  • Gene Expression Regulation / genetics*
  • Genes, Reporter
  • HeLa Cells
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D / genetics*
  • Heterogeneous-Nuclear Ribonucleoprotein D / physiology
  • Heterogeneous-Nuclear Ribonucleoprotein L / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics*
  • Homeostasis
  • Humans
  • Nonsense Mediated mRNA Decay / genetics*
  • RNA, Messenger / genetics
  • Ribonucleoproteins / genetics*
  • Ribonucleoproteins / physiology

Substances

  • 3' Untranslated Regions
  • HNRNPD protein, human
  • HNRPDL protein, human
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • Heterogeneous-Nuclear Ribonucleoprotein L
  • Heterogeneous-Nuclear Ribonucleoproteins
  • RNA, Messenger
  • Ribonucleoproteins