Large-scale analysis of the position-dependent binding and regulation of human RNA binding proteins

Abstract

Background: RNA binding proteins (RBPs) play essential roles in the regulation of RNA metabolism. Recent studies have disclosed that RBPs achieve their functions via binding to their targets in a position-dependent pattern on RNAs. However, few studies have systematically addressed the associations between the RBP’s functions and their positional binding preferences.

Methods: Here, we present large-scale analyses on the functional targets of human RBPs by integrating the enhanced cross-linking and immunoprecipitation followed by sequencing (eCLIP-seq) datasets and the shRNA knockdown followed by RNA-seq datasets that are deposited in the integrated ENCyclopedia of DNA Elements in the human genome (ENCODE) data portal.

Results: We found that (1) binding to the translation termination site and the 3′ untranslated region is important to most human RBPs in the RNA decay regulation; (2) RBPs’ binding and regulation follow a cell-type specific pattern.

Conclusions: These analysis results show the strong relationship between the binding position and the functions of RBPs, which provides novel insights into the RBPs’ regulation mechanisms.

Graphical abstract

Keywords

RNA binding protein / CLIP-seq / RNA-seq / knockdown / RNA regulation

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SUPPLEMENTARY MATERIALS

The supplementary materials can be found online with this article at https:// 10.1007/s40484-020-0206-5.

ACKNOWLEDGEMENTS

We thank members of the Ouyang Lab for discussions. We thank the ENCODE Consortium and Gene Yeo’s Lab from UCSD for generating the eCLIP data and Brenton Graveley’s Lab from UConn for generating the shRNA knockdown followed by RNA-seq data. Z.O. acknowledges the National Institute of General Medical Sciences (https://www.nigms.nih.gov/) grant R35GM124998. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

COMPLIANCE WITH ETHICS GUIDELINES

The authors Jianan Lin, and Zhengqing Ouyang declare that they have no conflict of interests.ƒ

All procedures performed in studies were in accordance with the ethical standards of the institution or practice at which the studies were conducted, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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