the rna-binding landscapes of two sr proteins reveal unique functions and binding to diverse rna classes两个sr蛋白的rna结合景观展示独特的功能和类绑定到不同的rna.pdfVIP

Änkö et al. Genome Biology 2012, 13:R17 /2012/13/3/R17 RESEARCH Open Access The RNA-binding landscapes of two SR proteins reveal unique functions and binding to diverse RNA classes 1,4* 1 1 3 3 1 Minna-Liisa Änkö , Michaela Müller-McNicoll , Holger Brandl , Tomaz Curk , Crtomir Gorup , Ian Henry , Jernej Ule2 and Karla M Neugebauer1* Abstract Background: The SR proteins comprise a family of essential, structurally related RNA binding proteins. The complexity of their RNA targets and specificity of RNA recognition in vivo is not well understood. Here we use iCLIP to globally analyze and compare the RNA binding properties of two SR proteins, SRSF3 and SRSF4, in murine cells. Results: SRSF3 and SRSF4 binding sites mapped to largely non-overlapping target genes, and in vivo consensus binding motifs were distinct. Interactions with intronless and intron-containing mRNAs as well as non-coding RNAs were detected. Surprisingly, both SR proteins bound to the 3’ ends of the majority of intronless histone transcripts, implicating SRSF3 and SRSF4 in histone mRNA metabolism. In contrast, SRSF3 but not SRSF4 specifically bound transcripts encoding numerous RNA binding proteins. Remarkably, SRSF3 was shown to modulate alternative splicing of its own as well as three other transcripts encoding SR proteins. These SRSF3-mediated splicing events led to downregulation of heterologous SR proteins via nonsense-mediated decay. Conclusions: SRSF3 and SRSF4 display unique RNA binding properties underlying diverse cellular regulatory mechanisms, with shared as well as unique coding and non-coding targets. Importantly, CLIP analysis led to the discovery that SRSF3 cross-regulates the expression of other SR prote