DDX1 regulates alternative splicing and insulin secretion in pancreatic β cells

Wen Zhong; Zonghong Li; Maoge Zhou; Tao Xu; You Wang

doi:10.1016/j.bbrc.2018.04.147

DDX1 regulates alternative splicing and insulin secretion in pancreatic β cells

Biochem Biophys Res Commun. 2018 Jun 7;500(3):751-757. doi: 10.1016/j.bbrc.2018.04.147. Epub 2018 Apr 23.

Authors

Wen Zhong¹, Zonghong Li², Maoge Zhou², Tao Xu³, You Wang⁴

Affiliations

¹ College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China; National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
² National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
³ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. Electronic address: xutao@ibp.ac.cn.
⁴ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. Electronic address: wangyou51@126.com.

PMID: 29679569
DOI: 10.1016/j.bbrc.2018.04.147

Abstract

DEAD-box helicase 1 (DDX1) is a multifunction protein involved in diverse cellular processes including transcription, viral replication, mRNA/miRNA processing, and tRNA splicing. Here, we report a novel function of DDX1 in mRNA alternative splicing in pancreatic β cells. By performing integrated data analysis of high-throughput RNA sequencing (RNA-Seq), and cross-linking and immunoprecipitation coupled with deep sequencing (CLIP-Seq), we identify hundreds of alternative splicing genes that are targeted by DDX1. These DDX1-targeted alternative splicing genes are mainly associated with calcium ion binding, high voltage-gated calcium channel, and transmembrane transporter. Functionally, silencing DDX1 impairs calcium influx and insulin secretion in the pancreatic β cells. These results reveal an important role for DDX1 in the regulation of gene alternative splicing and insulin secretion in pancreatic β cells.

Keywords: Alternative splicing; DDX1; Insulin; β cell.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alternative Splicing / genetics*
Cell Line
DEAD-box RNA Helicases / metabolism*
Gene Knockdown Techniques
Humans
Insulin / metabolism*
Insulin Secretion
Insulin-Secreting Cells / metabolism*
RNA / metabolism
Sequence Analysis, RNA

Substances

Insulin
RNA
DDX1 protein, human
DEAD-box RNA Helicases