A census of human RNA-binding proteins
Open accessAbstract
Post-transcriptional gene regulation (PTGR) concerns processes involved in the maturation, transport, stability and translation of coding and non-coding RNAs. RNA-binding proteins (RBPs) and ribonucleoproteins coordinate RNA processing and PTGR. The introduction of large-scale quantitative methods, such as next-generation sequencing and modern protein mass spectrometry, has renewed interest in the investigation of PTGR and the protein factors involved at a systems-biology level. Here, we present a census of 1,542 manually curated RBPs that we have analysed for their interactions with different classes of RNA, their evolutionary conservation, their abundance and their tissue-specific expression. Our analysis is a critical step towards the comprehensive characterization of proteins involved in human RNA metabolism.
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Effects of many RBPs on translation are yet to be identified.
“Nonetheless, effects of many RBPs on translation are yet to be identified [41].”
From Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis (2024) · cites this paper as [41]
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Gene Ontology: tool for the unification of biology
Ashburner, M., Ball, C. A., Blake, J. A., Botstein, D., Butler, H., Cherry, J. M., Davis, A. P., Dolinski, K., Dwight, S. S., Eppig, J. T., et al. (2000) · Nature Genetics · doi:10.1038/75556 · Cited by 43,206 · see citing works
RNA-Seq: a revolutionary tool for transcriptomics
Wang, Z., Gerstein, M., & Snyder, M. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2484 · Cited by 13,174 · see citing works
Global quantification of mammalian gene expression control
Schwanhäusser, B., Busse, D., Li, N., Dittmar, G., Schuchhardt, J., Wolf, J., Chen, W., & Selbach, M. (2011) · Nature · doi:10.1038/nature10098 · Cited by 6,566 · cited 1× · see citing works
“protein abundance in the cell as previously shown by large-scale transcriptomic and proteomic studies (Guo et al., 2010; Schwanhausser et al., 2011).”
BackgroundThe Pfam protein families database
Finn, R. D., Mistry, J., Tate, J., Coggill, P., Heger, A., Pollington, J. E., Gavin, O. L., Gunasekaran, P., Ceric, G., Forslund, K., et al. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp985 · Cited by 2,694 · see citing works
RNA sequencing: advances, challenges and opportunities
Ozsolak, F., & Milos, P. M. (2011) · Nature Reviews Genetics · doi:10.1038/nrg2934 · Cited by 2,135 · cited 3× · see citing works
“, 2014), small and long RNA-sequencing (Jan et al., 2011; Ozsolak and Milos, 2011; Wang et al., 2009), or 3’-end sequencing methods profiling of alternative polyadenylation sites and poly(A) tail lengths (Chang et al.”
BackgroundTranscriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology
Voineagu, I., Wang, X., Johnston, P., Lowe, J. K., Tian, Y., Horvath, S., Mill, J., Cantor, R. M., Blencowe, B. J., & Geschwind, D. H. (2011) · Nature · doi:10.1038/nature10110 · Cited by 1,874 · see citing works
Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1
Orr, H. T., Chung, M.-Y., Banfi, S., Kwiatkowski, T. J., Servadio, A., Beaudet, A. L., McCall, A. E., Duvick, L. A., Ranum, L. P. W., & Zoghbi, H. Y. (1993) · Nature Genetics · doi:10.1038/ng0793-221 · Cited by 1,632 · cited 1× · see citing works
“ATXN1, ATXN1L spinocerebellar ataxia polyglutamine expansion leading to protein aggregation (Banfi et al., 1994; Orr et al., 1993; Servadio et al., 1995) ATXN2, ATXN2L spinocerebellar ataxia, susceptibility to lateonset Parkinson disease, susceptibility to amyotrophic lateral sclerosis (ALS) polyglutamine expansion le…”
BackgroundA census of human transcription factors: function, expression and evolution
Vaquerizas, J. M., Kummerfeld, S. K., Teichmann, S. A., & Luscombe, N. M. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2538 · Cited by 1,573 · see citing works
A compendium of RNA-binding motifs for decoding gene regulation
Ray, D., Kazan, H., Cook, K. B., Weirauch, M. T., Najafabadi, H. S., Li, X., Gueroussov, S., Albu, M., Zheng, H., Yang, A., et al. (2013) · Nature · doi:10.1038/nature12311 · Cited by 1,480 · cited 2× · see citing works
“sites (Ascano et al., 2012a; Ray et al., 2013; Spencer et al., 2006; Todd et al., 2001), and the evolution of paralogs represent an alternative to facilitating regulation across cell types.”
BackgroundTranscriptional landscape of the prenatal human brain
Miller, J. A., Ding, S.-L., Sunkin, S. M., Smith, K. A., Ng, L., Szafer, A., Ebbert, A., Riley, Z. L., Royall, J. J., Aiona, K., et al. (2014) · Nature · doi:10.1038/nature13185 · Cited by 1,325 · see citing works
An Abundance of Ubiquitously Expressed Genes Revealed by Tissue Transcriptome Sequence Data
Ramsköld, D., Wang, E. T., Burge, C. B., & Sandberg, R. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000598 · Cited by 820 · see citing works
Landscape and variation of RNA secondary structure across the human transcriptome
Wan, Y., Qu, K., Zhang, Q. C., Flynn, R. A., Manor, O., Ouyang, Z., Zhang, J., Spitale, R. C., Snyder, M. P., Segal, E., et al. (2014) · Nature · doi:10.1038/nature12946 · Cited by 555 · see citing works
Neuronal regulation of alternative pre-mRNA splicing
Li, Q., Lee, J.-A., & Black, D. L. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2237 · Cited by 376 · see citing works
RNA Quality Control in Eukaryotes
Doma, M. K., & Parker, R. (2007) · Cell · doi:10.1016/j.cell.2007.10.041 · Cited by 345 · see citing works
The splicing regulator Rbfox1 (A2BP1) controls neuronal excitation in the mammalian brain
Gehman, L. T., Stoilov, P., Maguire, J., Damianov, A., Lin, C.-H., Shiue, L., Ares, M., Mody, I., & Black, D. L. (2011) · Nature Genetics · doi:10.1038/ng.841 · Cited by 331 · see citing works
Sequence-specific binding of single-stranded RNA: is there a code for recognition?
Auweter, S. D., Oberstrass, F. C., & Allain, F. H.-T. (2006) · Nucleic Acids Research · doi:10.1093/nar/gkl620 · Cited by 314 · see citing works
McKee, A. E., Minet, E., Stern, C., Riahi, S., Stiles, C. D., & Silver, P. A. (2005) · BMC Developmental Biology · doi:10.1186/1471-213x-5-14 · Cited by 166 · see citing works
Flagged first, then by citations
Research works printed but not linked: 32
- [3]3. Ascano M, Hafner M, Cekan P, Gerstberger S. & Tuschl T. Identification of RNA-protein interaction networks using PAR-CLIP. Wiley Interdiscip. Rev. RNA3, 159-177 (2011).
- [4]4. Gerstberger S, Hafner M. & Tuschl T. Learning the language of post-transcriptional gene regulation. Genome Biol. 14, 130 (2013). [PubMed: 23998708]
- [12]12. Tenenbaum SA, Carson CC, Lager PJ & Keene JD Identifying mRNA subsets in messenger ribonucleoprotein complexes by using cDNA arrays. Proc. Natl Acad. Sci. USA 97, 14085-14090 (2000). [PubMed: 11121017]
- [14]14. McHugh CA, Russell P. & Guttman M. Methods for comprehensive experimental identification of RNA-protein interactions. Genome Biol. 15, 203 (2014). [PubMed: 24467948]
- [32]32. Lunde BM, Moore C. & Varani G. RNA-binding proteins: modular design for efficient function. Nature Rev. Mol. Cell. Biol. 8, 479-490 (2007). [PubMed: 17473849] This review summarizes the most commonly found RBDs and gives an overview of their structural characteristics and binding modes.
- [38]38. Sommerville J. Activities of cold-shock domain proteins in translation control. Bioessays 21, 319325 (1999). [PubMed: 10377894]
- [59]59. Kechavarzi B. & Janga SC Dissecting the expression landscape of RNA-binding proteins in human cancers. Genome Biol. 15, R14 (2014). [PubMed: 24410894]
- [65]65. Klein C. & Westenberger A. Genetics of Parkinson's disease. Cold Spring Harb. Perspect. Med. 2, a008888 (2012).
- [66]66. Scheper GC, van der Knaap MS & Proud CG Translation matters: protein synthesis defects in inherited disease. Nature Rev. Genet. 8, 711-723 (2007). [PubMed: 17680008] This is a comprehensive review of mRNA-binding, tRNA-binding and ribosomal proteins involved in translation, genetic mutations of which cause human diseases.
- [82]82. Phipps KR, Charette JM & Baserga SJ The small subunit processome in ribosome biogenesis progress and prospects. Wiley Interdiscip. Rev. RNA 2, 1-21 (2011). [PubMed: 21318072]
- [84]84. Sibbritt T, Patel HR & Preiss T. Mapping and significance of the mRNA methylome. Wiley Interdiscip. Rev. RNA 4, 397-422 (2013). [PubMed: 23681756]
- [94]94. Freilich S. et al. Relationship between the tissue-specificity of mouse gene expression and the evolutionary origin and function of the proteins. Genome Biol. 6, R56 (2005). [PubMed: 15998445]
- [96]96. Dezso Z. et al. A comprehensive functional analysis of tissue specificity of human gene expression. BMC Biol. 6, 49 (2008). [PubMed: 19014478]
- [101]101. Castle JC et al. Digital genome-wide ncRNA expression, including snoRNAs, across 11 human tissues using polyA-neutral amplification. PLoS ONE 5, e11779 (2010).
- [102]102. Dittmar KA, Goodenbour JM & Pan T. Tissue-specific differences in human transfer RNA expression. PLoS Genet. 2, e221 (2006). [PubMed: 17194224]
- [110]110. Voronina E, Seydoux G, Sassone-Corsi P. & Nagamori I. RNA granules in germ cells. Cold Spring Harb. Perspect. Biol. 3, a002774 (2011).
- [116]116. Frost RJA et al. MOV10L1 is necessary for protection of spermatocytes against retrotransposons by PIWI-interacting RNAs. Proc. Natl Acad. Sci. USA 107, 11847-11852 (2010). [PubMed: 20547853]
- [117]117. Zheng K. et al. Mouse MOV10L1 associates with PIWI proteins and is an essential component of the PIWI-interacting RNA (piRNA) pathway. Proc. Natl Acad. Sci. USA 107, 11841-11846 (2010). [PubMed: 20534472]
- [119]119. Rosenberg HF in Ribonucleases Ch. 2 (ed. Nicholson AW) 35-53 (Springer, 2011).
- [143]143. Keene JD RNA regulons: coordination of post-transcriptional events. Nature Rev. Genet. 8, 533543 (2007). [PubMed: 17572691]
- [155]155. Cirillo D. et al. Constitutive patterns of gene expression regulated by RNA-binding proteins. Genome Biol. 15, R13 (2014). [PubMed: 24401680]
- [156]156. Mittal N, Roy N, Babu MM & Janga SC Dissecting the expression dynamics of RNA-binding proteins in posttranscriptional regulatory networks. Proc. Natl Acad. Sci. USA 106, 2030020305 (2009). [PubMed: 19918083]
- [160]160. MacDonald CC & McMahon KW Tissue-specific mechanisms of alternative polyadenylation: testis, brain, and beyond. Wiley Interdiscip. Rev. RNA1, 494-501 (2010).
- [163]163. Kee K, Angeles VT, Flores M, Nguyen HN & Reijo Pera RA Human DAZL, DAZ and BOULE genes modulate primordial germ-cell and haploid gamete formation. Nature 462, 222225 (2009). [PubMed: 19865085]
- [170]170. Mody M. et al. Genome-wide gene expression profiles of the developing mouse hippocampus. Proc. Natl Acad. Sci. USA 98, 8862-8867 (2001). [PubMed: 11438693]
- [176]176. Thiyagarajan N, Ferguson R, Subramanian V. & Acharya KR Structural and molecular insights into the mechanism of action of human angiogenin-ALS variants in neurons. Nature Commun. 3, 1121 (2012). [PubMed: 23047679]
- [178]178. Mukherjee N. et al. Global target mRNA specification and regulation by the RNA-binding protein ZFP36. Genome Biol. 15, R12 (2014). [PubMed: 24401661]
- [185]185. Ulitsky I. & Bartel DP lincRNAs: Genomics, evolution, and mechanisms. Cell 154, 26-46 (2013). [PubMed: 23827673] This is a detailed review on the emerging roles of lncRNAs in gene regulation.
- [195]195. Maraia RJ & Lamichhane TN 3 ′ processing of eukaryotic precursor tRNAs. Wiley Interdiscip. Rev. RNA 2, 362-375 (2011). [PubMed: 21572561]
- [198]198. Mroczek S. & Dziembowski A. U6 RNA biogenesis and disease association. Wiley Interdiscip. Rev. RNA 4, 581-592 (2013). [PubMed: 23776162]
- [204]204. Peterlin BM, Brogie JE & Price DH 7SK snRNA: a noncoding RNA that plays a major role in regulating eukaryotic transcription. Wiley Interdiscip. Rev. RNA 3, 92-103 (2011). [PubMed: 21853533]
- [205]205. Fox AH & Lamond AI Paraspeckles. Cold Spring Harb. Perspect. Biol. 2, a000687 (2010).
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- Authors
- Gerstberger, S., Hafner, M., & Tuschl, T.
- Affiliations
- Howard Hughes Medical Institute (US)
- National Institutes of Health (US)
- Corresponding author
- Tuschl, Thomas
- Venue
- Nature Reviews Genetics
- Published
- 2014-11-04
- Volume
- 15
- Issue
- 12
- Pages
- 829-845
- ISSN
- 1471-0056 (ISSN-L)
- 1471-0064
- PMC
- PMC11148870
- OpenAlex
- W1997535872
- Cited by
- 2,032
- References
- 17
- Citations by year
- 2026: 137 · 2025: 193 · 2024: 226 · 2023: 226 · 2022: 198 · 2021: 266 · 2020: 226 · 2019: 155 · 2018: 137 · 2017: 130 · 2016: 89 · 2015: 47 · 2014: 1
- FWCI
- 8.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons - RU (Rockefeller University) (submittedVersion, cc-by-nc-sa)
- Markus Library
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (Z99 AR999999)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- RNA-binding proteins, post-transcriptional regulation, ribonucleoprotein, RNA-protein interactions, evolutionary conservation, protein abundance, tissue-specific gene expression, RNA metabolism, human proteome
- MeSH terms
- Animals, Gene Expression Regulation, Humans, RNA, RNA-Binding Proteins
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