Königs et al. 2020 (PRJNA598359)

Title	RNA-Seq and Ribo-Seq of P19 WT and SRSF7-GFP overexpressing cells
Organism
Number of Samples	3
Release Date	2019/12/31 00:00
Sequencing Types
Protocol Details

GWIPS-viz	Trips-Viz

Title
Authors	Königs V,de Oliveira Freitas Machado C,Arnold B,Blümel N,Solovyeva A,Löbbert S,Schafranek M,Ruiz De Los Mozos I,Wittig I,McNicoll F,Schulz MH,Müller-McNicoll M
Journal	Nature structural & molecular biology
Publication Date	2020 Mar
Abstract	SRSF7 is an essential RNA-binding protein whose misexpression promotes cancer. Here, we describe how SRSF7 maintains its protein homeostasis in murine P19 cells using an intricate negative feedback mechanism. SRSF7 binding to its premessenger RNA promotes inclusion of a poison cassette exon and transcript degradation via nonsense-mediated decay (NMD). However, elevated SRSF7 levels inhibit NMD and promote translation of two protein halves, termed Split-ORFs, from the bicistronic SRSF7-PCE transcript. The first half acts as dominant-negative isoform suppressing poison cassette exon inclusion and instead promoting the retention of flanking introns containing repeated SRSF7 binding sites. Massive SRSF7 binding to these sites and its oligomerization promote the assembly of large nuclear bodies, which sequester SRSF7 transcripts at their transcription site, preventing their export and restoring normal SRSF7 protein levels. We further show that hundreds of human and mouse NMD targets, especially RNA-binding proteins, encode potential Split-ORFs, some of which are expressed under specific cellular conditions.
PMC	PMC7096898
PMID	32123389
DOI

ⓘ For more Information on the columns shown here see: About