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Large-scale analysis of the position-dependent binding and regulation of human RNA binding proteins |
Jianan Lin1,2, Zhengqing Ouyang1( ) |
1. Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA 01003, USA 2. Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA |
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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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Keywords
RNA binding protein
CLIP-seq
RNA-seq
knockdown
RNA regulation
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Corresponding Author(s):
Zhengqing Ouyang
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Online First Date: 10 June 2020
Issue Date: 13 July 2020
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|
1 |
J. D. Keene, (2007) RNA regulons: coordination of post-transcriptional events. Nat. Rev. Genet., 8, 533–543
https://doi.org/10.1038/nrg2111
pmid: 17572691
|
2 |
D. D. Licatalosi, , A. Mele, , J. J. Fak, , J. Ule, , M. Kayikci, , S. W. Chi, , T. A. Clark, , A. C. Schweitzer, , J. E. Blume, , X. Wang, , et al. (2008) HITS-CLIP yields genome-wide insights into brain alternative RNA processing. Nature, 456, 464–469
https://doi.org/10.1038/nature07488
pmid: 18978773
|
3 |
D. I. Kao, , G. M. Aldridge, , I. J. Weiler, and W. T. Greenough, (2010) Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein. Proc. Natl. Acad. Sci. USA, 107, 15601–15606
https://doi.org/10.1073/pnas.1010564107
pmid: 20713728
|
4 |
O. D. King, , A. D. Gitler, and J. Shorter, (2012) The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res., 1462, 61–80
https://doi.org/10.1016/j.brainres.2012.01.016
pmid: 22445064
|
5 |
C. Lagier-Tourenne, , M. Polymenidou, and D. W. Cleveland, (2010) TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration. Hum. Mol. Genet., 19, R46–R64
https://doi.org/10.1093/hmg/ddq137
pmid: 20400460
|
6 |
K. E. Lukong, , K. W. Chang, , E. W. Khandjian, and S. Richard, (2008) RNA-binding proteins in human genetic disease. Trends Genet., 24, 416–425
https://doi.org/10.1016/j.tig.2008.05.004
pmid: 18597886
|
7 |
J. König, , K. Zarnack, , N. M. Luscombe, and J. Ule, (2012) Protein-RNA interactions: new genomic technologies and perspectives. Nat. Rev. Genet., 13, 77–83
https://doi.org/10.1038/nrg3141
pmid: 22251872
|
8 |
M. Hafner, , M. Landthaler, , L. Burger, , M. Khorshid, , J. Hausser, , P. Berninger, , A. Rothballer, , M. Ascano, Jr, A. C. Jungkamp, , M. Munschauer, , et al. (2010) Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP. Cell, 141, 129–141
https://doi.org/10.1016/j.cell.2010.03.009
pmid: 20371350
|
9 |
J. König, , K. Zarnack, , G. Rot, , T. Curk, , M. Kayikci, , B. Zupan, , D. J. Turner, , N. M. Luscombe, and J. Ule, (2010) iCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution. Nat. Struct. Mol. Biol., 17, 909–915
https://doi.org/10.1038/nsmb.1838
pmid: 20601959
|
10 |
K. B. Cook, , T. R. Hughes, and Q. D. Morris, (2015) High-throughput characterization of protein-RNA interactions. Brief. Funct. Genomics, 14, 74–89
https://doi.org/10.1093/bfgp/elu047
pmid: 25504152
|
11 |
B. Chen, , J. Yun, , M. S. Kim, , J. T. Mendell, and Y. Xie, (2014) PIPE-CLIP: a comprehensive online tool for CLIP-seq data analysis. Genome Biol., 15, R18
https://doi.org/10.1186/gb-2014-15-1-r18
pmid: 24451213
|
12 |
T. Wang, , Y. Xie, and G. Xiao, (2014) dCLIP: a computational approach for comparative CLIP-seq analyses. Genome Biol., 15, R11
https://doi.org/10.1186/gb-2014-15-1-r11
pmid: 24398258
|
13 |
T. Wang, , B. Chen, , M. Kim, , Y. Xie, and G. Xiao, (2014) A model-based approach to identify binding sites in CLIP-Seq data. PLoS One, 9, e93248
https://doi.org/10.1371/journal.pone.0093248
pmid: 24714572
|
14 |
M. T. Lovci, , D. Ghanem, , H. Marr, , J. Arnold, , S. Gee, , M. Parra, , T. Y. Liang, , T. J. Stark, , L. T. Gehman, , S. Hoon, , et al. (2013) Rbfox proteins regulate alternative mRNA splicing through evolutionarily conserved RNA bridges. Nat. Struct. Mol. Biol., 20, 1434–1442
https://doi.org/10.1038/nsmb.2699
pmid: 24213538
|
15 |
S. Althammer, , J. González-Vallinas, , C. Ballaré, , M. Beato, and E. Eyras, (2011) Pyicos: a versatile toolkit for the analysis of high-throughput sequencing data. Bioinformatics, 27, 3333–3340
https://doi.org/10.1093/bioinformatics/btr570
pmid: 21994224
|
16 |
P. J. Uren, , E. Bahrami-Samani, , S. C. Burns, , M. Qiao, , F. V. Karginov, , E. Hodges, , G. J. Hannon, , J. R. Sanford, , L. O. Penalva, and A. D. Smith, (2012) Site identification in high-throughput RNA-protein interaction data. Bioinformatics, 28, 3013–3020
https://doi.org/10.1093/bioinformatics/bts569
pmid: 23024010
|
17 |
F. Comoglio, , C. Sievers, and R. Paro, (2015) Sensitive and highly resolved identification of RNA-protein interaction sites in PAR-CLIP data. BMC Bioinformatics, 16, 32
https://doi.org/10.1186/s12859-015-0470-y
pmid: 25638391
|
18 |
D. L. Corcoran, , S. Georgiev, , N. Mukherjee, , E. Gottwein, , R. L. Skalsky, , J. D. Keene, and U. Ohler, (2011) PARalyzer: definition of RNA binding sites from PAR-CLIP short-read sequence data. Genome Biol., 12, R79
https://doi.org/10.1186/gb-2011-12-8-r79
pmid: 21851591
|
19 |
M. J. Moore, , C. Zhang, , E. C. Gantman, , A. Mele, , J. C. Darnell, and R. B. Darnell, (2014) Mapping Argonaute and conventional RNA-binding protein interactions with RNA at single-nucleotide resolution using HITS-CLIP and CIMS analysis. Nat. Protoc., 9, 263–293
https://doi.org/10.1038/nprot.2014.012
pmid: 24407355
|
20 |
A. Shah, , Y. Qian, , S. M. Weyn-Vanhentenryck, and C. Zhang, (2017) CLIP Tool Kit (CTK): a flexible and robust pipeline to analyze CLIP sequencing data. Bioinformatics, 33, 566–567
pmid: 27797762
|
21 |
F. Erhard, , L. Dölken, , L. Jaskiewicz, and R. Zimmer, (2013) PARma: identification of microRNA target sites in AGO-PAR-CLIP data. Genome Biol., 14, R79
https://doi.org/10.1186/gb-2013-14-7-r79
pmid: 23895117
|
22 |
J. Lin, , Y. Zhang, , W. N. Frankel, and Z. Ouyang, (2019) PRAS: Predicting functional targets of RNA binding proteins based on CLIP-seq peaks. PLOS Comput. Biol., 15, e1007227
https://doi.org/10.1371/journal.pcbi.1007227
pmid: 31425505
|
23 |
G. Rot, , Z. Wang, , I. Huppertz, , M. Modic, , T. Lenče, , M. Hallegger, , N. Haberman, , T. Curk, , C. von Mering, and J. Ule, (2017) High-resolution RNA maps suggest common principles of splicing and polyadenylation regulation by TDP-43. Cell Reports, 19, 1056–1067
https://doi.org/10.1016/j.celrep.2017.04.028
pmid: 28467899
|
24 |
E. T. Wang, , A. J. Ward, , J. M. Cherone, , J. Giudice, , T. T. Wang, , D. J. Treacy, , N. J. Lambert, , P. Freese, , T. Saxena, , T. A. Cooper, , et al. (2015) Antagonistic regulation of mRNA expression and splicing by CELF and MBNL proteins. Genome Res., 25, 858–871
https://doi.org/10.1101/gr.184390.114
pmid: 25883322
|
25 |
E. L. Van Nostrand, , G. A. Pratt, , A. A. Shishkin, , C. Gelboin-Burkhart, , M. Y. Fang, , B. Sundararaman, , S. M. Blue, , T. B. Nguyen, , C. Surka, , K. Elkins, , et al. (2016) Robust transcriptome-wide discovery of RNA-binding protein binding sites with enhanced CLIP (eCLIP). Nat. Methods, 13, 508–514
https://doi.org/10.1038/nmeth.3810
pmid: 27018577
|
26 |
E. L. Van Nostrand, , P. Freese, , G. A. Pratt, , X. Wang, , X. Wei, , R. Xiao, , S. M. Blue, , J.-Y. Chen, , N. A. L. Cody, , D. Dominguez, , et al. (2018) A large-scale binding and functional map of human RNA binding proteins. bioRxiv, 179648
|
27 |
M. I. Love, , W. Huber, and S. Anders, (2014) Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15, 550
https://doi.org/10.1186/s13059-014-0550-8
pmid: 25516281
|
28 |
J. L. Wagnon, , M. Briese, , W. Sun, , C. L. Mahaffey, , T. Curk, , G. Rot, , J. Ule, and W. N. Frankel, (2012) CELF4 regulates translation and local abundance of a vast set of mRNAs, including genes associated with regulation of synaptic function. PLoS Genet., 8, e1003067
https://doi.org/10.1371/journal.pgen.1003067
pmid: 23209433
|
29 |
C. A. Chénard, and S. Richard, (2008) New implications for the QUAKING RNA binding protein in human disease. J. Neurosci. Res., 86, 233–242
https://doi.org/10.1002/jnr.21485
pmid: 17787018
|
30 |
R. Gherzi, , K.-Y. Lee, , P. Briata, , D. Wegmüller, , C. Moroni, , M. Karin, and C.-Y. Chen, (2004) A KH domain RNA binding protein, KSRP, promotes ARE-directed mRNA turnover by recruiting the degradation machinery. Mol. Cell, 14, 571–583
https://doi.org/10.1016/j.molcel.2004.05.002
pmid: 15175153
|
31 |
S. Lebedeva, , M. Jens, , K. Theil, , B. Schwanhäusser, , M. Selbach, , M. Landthaler, and N. Rajewsky, (2011) Transcriptome-wide analysis of regulatory interactions of the RNA-binding protein HuR. Mol. Cell, 43, 340–352. PMID:21723171
https://doi.org/10.1016/j.molcel.2011.06.008
|
32 |
J. R. Hogg, and S. P. Goff, (2010) Upf1 senses 3′ UTR length to potentiate mRNA decay. Cell, 143, 379–389
|
33 |
The ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature, 489,57–74
|
34 |
C. A. Davis, , B. C. Hitz, , C. A. Sloan, , E. T. Chan, , J. M. Davidson, , I. Gabdank, , J. A. Hilton, , K. Jain, , U. K. Baymuradov, , A. K. Narayanan, , et al. (2018) The Encyclopedia of DNA elements (ENCODE): data portal update. Nucleic Acids Res., 46, D794–D801
https://doi.org/10.1093/nar/gkx1081
pmid: 29126249
|
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