Nuclear matrix factor hnRNP U/SAF-A exerts a global control of alternative splicing by regulating U2 snRNP maturation.
The nuclear matrix-associated hnRNP U/SAF-A protein has been implicated in diverse pathways from transcriptional regulation to telomere length control to X inactivation, but the precise mechanism underlying each of these processes has remained elusive. Here, we report hnRNP U as a regulator of SMN2 splicing from a custom RNAi screen. Genome-wide analysis by CLIP-seq reveals that hnRNP U binds virtually to all classes of regulatory noncoding RNAs, including all snRNAs required for splicing of both major and minor classes of introns, leading to the discovery that hnRNP U regulates U2 snRNP maturation and Cajal body morphology in the nucleus. Global analysis of hnRNP U-dependent splicing by RNA-seq coupled with bioinformatic analysis of associated splicing signals suggests a general rule for splice site selection through modulating the core splicing machinery. These findings exemplify hnRNP U/SAF-A as a potent regulator of nuclear ribonucleoprotein particles in diverse gene expression pathways.
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Rui
R
Xiao
Peng
P
Tang
Bo
B
Yang
Jie
J
Huang
Yu
Y
Zhou
Changwei
C
Shao
Hairi
H
Li
Hui
H
Sun
Yi
Y
Zhang
Xiang-Dong
XD
Fu
D017398:Alternative Splicing; D020541:Coiled Bodies / Q000378:metabolism; D006367:HeLa Cells; D034722:Heterogeneous-Nuclear Ribonucleoprotein U / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D013058:Mass Spectrometry; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000378:metabolism*; D055540:Survival of Motor Neuron 2 Protein / Q000235:genetics
D034722:Heterogeneous-Nuclear Ribonucleoprotein U; D017413:Ribonucleoprotein, U2 Small Nuclear; C526477:SMN2 protein, human; D055540:Survival of Motor Neuron 2 Protein