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.
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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.
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The authors Jianan Lin and Zhengqing Ouyang declare that they have no conflict of interests.
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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Author summary: RBPs are essential to the post-transcriptional processes, which include RNA stabilization, degradation, alternative splicing, localization, etc. To achieve these functions, RBPs bind to their target RNAs in a position-dependent manner. By applying a recently developed computational tool to a large number of human RBPs, we discover the important relationships between the binding in the 3′ untranslated region and the regulation of RNA abundance. In addition, we report the cell-type specific binding and regulation of RBPs. This systematical study sheds light on the mechanisms of RBPs in regulating RNA metabolism
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Lin, J., Ouyang, Z. Large-scale analysis of the position-dependent binding and regulation of human RNA binding proteins. Quant Biol 8, 119–129 (2020). https://doi.org/10.1007/s40484-020-0206-5
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DOI: https://doi.org/10.1007/s40484-020-0206-5