Widespread binding of FUS along nascent RNA regulates alternative splicing in the brain

Citations Over TimeTop 10% of 2012 papers

Abstract

Fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43) are RNA-binding proteins pathogenetically linked to amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), but it is not known if they regulate the same transcripts. We addressed this question using crosslinking and immunoprecipitation (iCLIP) in mouse brain, which showed that FUS binds along the whole length of the nascent RNA with limited sequence specificity to GGU and related motifs. A saw-tooth binding pattern in long genes demonstrated that FUS remains bound to pre-mRNAs until splicing is completed. Analysis of FUS(-/-) brain demonstrated a role for FUS in alternative splicing, with increased crosslinking of FUS in introns around the repressed exons. We did not observe a significant overlap in the RNA binding sites or the exons regulated by FUS and TDP-43. Nevertheless, we found that both proteins regulate genes that function in neuronal development.

Related Papers

• → Excision of the Sinorhizobium meliloti Group II Intron RmInt1 as Circles in Vivo(2006)45 cited
• → Exon and protein positioning in a pre-catalytic group II intron RNP primed for splicing(2020)12 cited
• → Preferential excision of the 5' proximal intron from mRNA precursors with two introns as mediated by the cap structure.(1987)117 cited
• → A maturase-encoding group MA intron of yeast mitochondria self-splices in vitro(1992)36 cited
• → Splicing of a Bacterial Group II Intron from Bacillus megaterium Is Independent of Intron-Encoded Protein(2009)2 cited