Sequence search and analysis of gene products containing RNA recognition motifs in the human genome

BMC Genomics

Ramanathan Sowdhamini¹  Sony Malhotra¹ 

[1]National Centre for Biological Sciences (TIFR), GKVK Campus, Bellary Road, Bangalore 560 065, India

关键词: Splicing;    Domain architecture;    Genome-wide survey;    Homo sapiens;    RNA recognition motif;   

Others  :  1121592
DOI  :  10.1186/1471-2164-15-1159

 received in 2014-07-29, accepted in 2014-12-12,  发布年份 2014

【 摘 要 】

Background

Gene expression is tightly regulated at both transcriptional and post-transcriptional levels. RNA-binding proteins are involved in post-transcriptional gene regulation events. They are involved in a variety of functions such as splicing, alternative splicing, nuclear import and export of mRNA, RNA stability and translation. There are several well-characterized RNA-binding motifs present in a whole genome, such as RNA recognition motif (RRM), KH domain, zinc-fingers etc. In the present study, we have investigated human genome for the presence of RRM-containing gene products starting from RRM domains in the Pfam (Protein family database) repository.

Results

In Pfam, seven families are recorded to contain RRM-containing proteins. We studied these families for their taxonomic representation, sequence features (identity, length, phylogeny) and structural properties (mapping conservation on the structures). We then examined the presence of RRM-containing gene products in Homo sapiens genome and identified 928 RRM-containing gene products. These were studied for their predicted domain architectures, biological processes, involvement in pathways, disease relevance and disorder content. RRM domains were observed to occur multiple times in a single polypeptide. However, there are 56 other co-existing domains involved in different regulatory functions. Further, functional enrichment analysis revealed that RRM-containing gene products are mainly involved in biological functions such as mRNA splicing and its regulation.

Conclusions

Our sequence analysis identified RRM-containing gene products in the human genome and provides insights into their domain architectures and biological functions. Since mRNA splicing and gene regulation are important in the cellular machinery, this analysis provides an early overview of genes that carry out these functions.

【 授权许可】

   
2014 Malhotra and Sowdhamini; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

【 参考文献 】

• [1]Latchman D: Gene Regulation. 2007. [Garland Science]
• [2]Le Jeune E, Ladurner AG: Analysing gene expression, edited by S. Lorkowski and P. Cullen. Protein Sci Publ Protein Soc 2004, 13:1950-1952.
• [3]Jackson DA, Pombo A, Iborra F: The balance sheet for transcription: an analysis of nuclear RNA metabolism in mammalian cells. FASEB J Off Publ Fed Am Soc Exp Biol 2000, 14:242-254.
• [4]Ambrose CM, Duyao MP, Barnes G, Bates GP, Lin CS, Srinidhi J, Baxendale S, Hummerich H, Lehrach H, Altherr M: Structure and expression of the Huntington’s disease gene: evidence against simple inactivation due to an expanded CAG repeat. Somat Cell Mol Genet 1994, 20:27-38.
• [5]Aerts S, Cools J: Cancer: Mutations close in on gene regulation. Nature 2013, 499:35-36.
• [6]Madhamshettiwar PB, Maetschke SR, Davis MJ, Reverter A, Ragan MA: Gene regulatory network inference: evaluation and application to ovarian cancer allows the prioritization of drug targets. Genome Med 2012, 4:41. BioMed Central Full Text
• [7]Cléry A, Blatter M, Allain FH-T: RNA recognition motifs: boring? Not quite. Curr Opin Struct Biol 2008, 18:290-298.
• [8]Burd CG, Dreyfuss G: Conserved structures and diversity of functions of RNA-binding proteins. Science 1994, 265:615-621.
• [9]FROM STRUCTURE TO FUNCTION OF RNA BINDING DOMAINS [http://www.ncbi.nlm.nih.gov/books/NBK63528/ webcite
• [10]King OD, Gitler AD, Shorter J: The tip of the iceberg: RNA-binding proteins with prion-like domains in neurodegenerative disease. Brain Res 2012, 1462:61-80.
• [11]Birney E, Kumar S, Krainer AR: Analysis of the RNA-recognition motif and RS and RGG domains: conservation in metazoan pre-mRNA splicing factors. Nucleic Acids Res 1993, 21:5803-5816.
• [12]Gamberi C, Johnstone O, Lasko P: Drosophila RNA binding proteins. Int Rev Cytol 2006, 248:43-139.
• [13]Kerner P, Degnan SM, Marchand L, Degnan BM, Vervoort M: Evolution of RNA-binding proteins in animals: insights from genome-wide analysis in the sponge Amphimedon queenslandica. Mol Biol Evol 2011, 28:2289-2303.
• [14]Tamburino AM, Ryder SP, Walhout AJM: A compendium of Caenorhabditis elegans RNA binding proteins predicts extensive regulation at multiple levels. G3 Bethesda Md 2013, 3:297-304.
• [15]Lorković ZJ, Barta A: Genome analysis: RNA recognition motif (RRM) and K homology (KH) domain RNA-binding proteins from the flowering plant Arabidopsis thaliana. Nucleic Acids Res 2002, 30:623-635.
• [16]McKee AE, Minet E, Stern C, Riahi S, Stiles CD, Silver PA: A genome-wide in situ hybridization map of RNA-binding proteins reveals anatomically restricted expression in the developing mouse brain. BMC Dev Biol 2005, 5:14. BioMed Central Full Text
• [17]Bateman A, Birney E, Durbin R, Eddy SR, Howe KL, Sonnhammer EL: The Pfam protein families database. Nucleic Acids Res 2000, 28:263-266.
• [18]Bateman A, Coin L, Durbin R, Finn RD, Hollich V, Griffiths-Jones S, Khanna A, Marshall M, Moxon S, Sonnhammer ELL, Studholme DJ, Yeats C, Eddy SR: The Pfam protein families database. Nucleic Acids Res 2004, 32(suppl 1):D138-D141.
• [19]Finn RD, Mistry J, Tate J, Coggill P, Heger A, Pollington JE, Gavin OL, Gunasekaran P, Ceric G, Forslund K, Holm L, Sonnhammer ELL, Eddy SR, Bateman A: The Pfam protein families database. Nucleic Acids Res 2009, 38(Database):D211-D222.
• [20]Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, Boursnell C, Pang N, Forslund K, Ceric G, Clements J, Heger A, Holm L, Sonnhammer ELL, Eddy SR, Bateman A, Finn RD: The Pfam protein families database. Nucleic Acids Res 2012, 40:D290-D301.
• [21]Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994, 22:4673-4680.
• [22]Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG: Clustal W and Clustal X version 2.0. Bioinformatics 2007, 23:2947-2948.
• [23]Guindon S, Dufayard J-F, Lefort V, Anisimova M, Hordijk W, Gascuel O: New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. Syst Biol 2010, 59:307-321.
• [24]Edgar RC: MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 2004, 32:1792-1797.
• [25]Tamura K, Stecher G, Peterson D, Filipski A, Kumar S: MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0. Mol Biol Evol 2013, 30:2725-2729.
• [26]Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The protein data bank. Nucleic Acids Res 2000, 28:235-242.
• [27]ConSurf 2010: calculating evolutionary conservation in sequence and structure of proteins and nucleic acids http://nar.oxfordjournals.org/content/38/suppl_2/W529.short webcite
• [28]Marchler-Bauer A, Panchenko AR, Shoemaker BA, Thiessen PA, Geer LY, Bryant SH: CDD: a database of conserved domain alignments with links to domain three-dimensional structure. Nucleic Acids Res 2002, 30:281-283.
• [29]Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ: Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997, 25:3389-3402.
• [30]Eddy SR: Accelerated profile HMM searches. PLoS Comput Biol 2011, 7:e1002195.
• [31]BLASTclust http://toolkit.tuebingen.mpg.de/blastclust# webcite
• [32]NCBI News: Spring 2004BLASTLab NCBI News: Spring 2004BLASTLab NCBI News: Spring 2004BLASTLab
• [33]Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000, 25:25-29.
• [34]Shamoo Y, Abdul-Manan N, Williams KR: Multiple RNA binding domains (RBDs) just don’t add up. Nucleic Acids Res 1995, 23:725-728.
• [35]Huang DW, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009, 4:44-57.
• [36]Huang DW, Sherman BT, Lempicki RA: Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 2009, 37:1-13.
• [37]Kanehisa M, Goto S: KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res 2000, 28:27-30.
• [38]Castello A, Fischer B, Hentze MW, Preiss T: RNA-binding proteins in Mendelian disease. Trends Genet TIG 2013, 29:318-327.
• [39]Ward JJ, McGuffin LJ, Bryson K, Buxton BF, Jones DT: The DISOPRED server for the prediction of protein disorder. Bioinformatics 2004, 20:2138-2139.
• [40]Gray DA, Woulfe J: Structural disorder and the loss of RNA homeostasis in aging and neurodegenerative disease. Front Genet 2013, 4:149.
• [41]Vanderweyde T, Youmans K, Liu-Yesucevitz L, Wolozin B: Role of stress granules and RNA-binding proteins in neurodegeneration: a mini-review. Gerontology 2013, 59:524-533.
• [42]Wolozin B: Regulated protein aggregation: stress granules and neurodegeneration. Mol Neurodegener 2012, 7:56. BioMed Central Full Text
• [43]Daubner GM, Cléry A, Allain FH-T: RRM–RNA recognition: NMR or crystallography…and new findings. Curr Opin Struct Biol 2013, 23:100-108. [Folding and Binding / Protein-Nucleic Acid Interactions]
• [44]Maris C, Dominguez C, Allain FH-T: The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression. FEBS J 2005, 272:2118-2131.
• [45]Castello A, Fischer B, Eichelbaum K, Horos R, Beckmann BM, Strein C, Davey NE, Humphreys DT, Preiss T, Steinmetz LM, Krijgsveld J, Hentze MW: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 2012, 149:1393-1406.
• [46]Tompa P, Csermely P: The role of structural disorder in the function of RNA and protein chaperones. FASEB J 2004, 18:1169-1175.
• [47]Korneta I, Bujnicki JM: Intrinsic disorder in the human spliceosomal proteome. PLoS Comput Biol 2012, 8:e1002641.
• [48]Lukong KE, Chang K, Khandjian EW, Richard S: RNA-binding proteins in human genetic disease. Trends Genet TIG 2008, 24:416-425.
• [49]FigTree http://tree.bio.ed.ac.uk/software/figtree/ webcite
• [50]Ren J, Wen L, Gao X, Jin C, Xue Y, Yao X: DOG 1.0: illustrator of protein domain structures. Cell Res 2009, 19:271-273.
• [51]Hamosh A, Scott AF, Amberger JS, Bocchini CA, McKusick VA: Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res 2005, 33(suppl 1):D514-D517.