Natural antisense transcripts with coding capacity in Arabidopsismay have a regulatory role that is not linked to double-stranded RNA degradation
Tóm tắt
Overlapping transcripts in antisense orientation have the potential to form double-stranded RNA (dsRNA), a substrate for a number of different RNA-modification pathways. One prominent route for dsRNA is its breakdown by Dicer enzyme complexes into small RNAs, a pathway that is widely exploited by RNA interference technology to inactivate defined genes in transgenic lines. The significance of this pathway for endogenous gene regulation remains unclear. We have examined transcription data for overlapping gene pairs in Arabidopsis thaliana. On the basis of an analysis of transcripts with coding regions, we find the majority of overlapping gene pairs to be convergently overlapping pairs (COPs), with the potential for dsRNA formation. In all tissues, COP transcripts are present at a higher frequency compared to the overall gene pool. The probability that both the sense and antisense copy of a COP are co-transcribed matches the theoretical value for coexpression under the assumption that the expression of one partner does not affect the expression of the other. Among COPs, we observe an over-representation of spliced (intron-containing) genes (90%) and of genes with alternatively spliced transcripts. For loci where antisense transcripts overlap with sense transcript introns, we also find a significant bias in favor of alternative splicing and variation of polyadenylation. The results argue against a predominant RNA degradation effect induced by dsRNA formation. Instead, our data support alternative roles for dsRNAs. They suggest that at least for a subgroup of COPs, antisense expression may induce alternative splicing or polyadenylation.
Tài liệu tham khảo
Boi S, Solda G, Tenchini ML: Shedding light on the dark side of the genome: overlapping genes in higher eukaryotes. Curr Genomics. 2004, 5: 509-524. 10.2174/1389202043349020.
Fahey ME, Moore TF, Higgins DG: Overlapping antisense transcription in the human genome. Comp Funct Genomics. 2002, 3: 244-253. 10.1002/cfg.173.
Lehner B, Williams G, Campbell RD, Sanderson CM: Antisense transcripts in the human genome. Trends Genet. 2002, 18: 63-65. 10.1016/S0168-9525(02)02598-2.
Wagner EGH, Flardh K: Antisense RNAs everywhere?. Trends Genet. 2002, 18: 223-226. 10.1016/S0168-9525(02)02658-6.
Hastings ML, Milcarek C, Martincic K, Peterson ML, Munroe SH: Expression of the thyroid hormone receptor gene, erbAα, in B lymphocytes: alternative mRNA processing is independent of differentiation but correlates with antisense RNA levels. Nucleic Acids Res. 1997, 25: 4296-4300. 10.1093/nar/25.21.4296.
Edgar A: The gene structure and expression of human ABHD1: overlapping polyadenylation signal sequence with Sec12. BMC Genomics. 2003, 4: 18-10.1186/1471-2164-4-18.
Gray TA, Azama K, Whitmore K, Min A, Abe S, Nicholls RD: Phylogenetic conservation of the Makorin-2 gene, encoding a multiple zinc-finger protein, antisense to the RAF1 proto-oncogene. Genomics. 2001, 77: 119-126. 10.1006/geno.2001.6627.
Chu J, Dolnick BJ: Natural antisense (rTS[α]) RNA induces site-specific cleavage of thymidylate synthase mRNA. Biochim Biophys Acta. 2002, 1587: 183-193. 10.1016/S0925-4439(02)00081-9.
Aravin AA, Naumova NM, Tulin AV, Vagin VV, Rozovsky YM, Gvozdev VA: Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Curr Biol. 2001, 11: 1017-1027. 10.1016/S0960-9822(01)00299-8.
Li AW, Murphy PR: Erratum to expression of alternatively spliced FGF-2 antisense RNA transcripts in the central nervous system: regulation of FGF-2 mRNA translation. Mol Cell Endocrinol. 2000, 170: 231-242. 10.1016/S0303-7207(00)00440-8.
Bass BL, Weintraub H: An unwinding activity that covalently modifies its double-stranded RNA substrate. Cell. 1988, 55: 1089-1098. 10.1016/0092-8674(88)90253-X.
Zhang Z, Carmichael GG: The fate of dsRNA in the nucleus: a p54nrb-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell. 2001, 106: 465-475. 10.1016/S0092-8674(01)00466-4.
Vanhee-Brossollet C, Vaquero C: Do natural antisense transcripts make sense in eukaryotes?. Gene. 1998, 211: 1-9. 10.1016/S0378-1119(98)00093-6.
Gene Expression Omnibus. [http://www.ncbi.nlm.nih.gov/geo]
Barrett T, Suzek TO, Troup DB, Wilhite SE, Ngau WC, Ledoux P, Rudnev D, Lash AE, Fujibuchi W, Edgar R: NCBI GEO: mining millions of expression profiles - database and tools. Nucleic Acids Res. 2005, D562-D566. 33 Database
Craigon D, James N, Okyere J, Higgins J, Jotham J, May S: NASCArrays: a repository for microarray data generated by NASC's transcriptomics service. Nucleic Acid Res. 2004, D575-D577. 10.1093/nar/gkh133. 32 Database
NASCA Arrays: Affymetrix ATH1 arrays database. [http://affymetrix.arabidopsis.info/narrays/experimentbrowse.pl]
Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC: Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature. 1998, 391: 806-811. 10.1038/35888.
Lavorgna G, Dahary D, Lehner B, Sorek R, Sanderson CM, Casari G: In search of antisense. Trends Biochem Sci. 2004, 29: 88-94. 10.1016/j.tibs.2003.12.002.
Gunasekera AM, Patankar S, Schug J, Eisen G, Kissinger J, Roos D, Wirth DF: Widespread distribution of antisense transcripts in the Plasmodium falciparum genome. Mol Biochem Parasitol. 2004, 136: 35-42. 10.1016/j.molbiopara.2004.02.007.
Bauren G, Belikov S, Wieslander L: Transcriptional termination in the Balbiani ring 1gene is closely coupled to 3'-end formation and excision of the 3'-terminal intron. Genes Dev. 1998, 12: 2759-2769.
Wang X-J, Gaasterland T, Chua N-H: Genome-wide prediction and identification of cis-natural antisense transcripts in Arabidopsis thaliana. Genome Biol. 2005, 6: R30-10.1186/gb-2005-6-4-r30.
Kiyosawa H, Yamanaka I, Osato N, Kondo S, Hayashizaki Y: Antisense transcripts with FANTOM2 clone set and their implications for gene regulation. Genome Res. 2003, 13: 1324-1334. 10.1101/gr.982903.
TAIR ftp website. [ftp://ftp.arabidopsis.org/Maps/seqviewer_data/sv_gene_feature.data]
DuBois P: MySQL. 2000, Indianapolis, IN: New Riders Publishing
TIGR rice: rice expression database. [http://www.tigr.org/tdb/e2k1/osa1/expression/alt_spliced.info.shtml]
O. sativa database. [ftp://ftp.tigr.org/pub/data/Eukaryotic_Projects/o_sativa/annotation_dbs/pseudomolecules/version_3.0/all_chrs/all.TU_model.brief_info.3.1]
Ihaka R, Gentlement G: R:A language for data analysis and graphics. J Comp Graph Statist. 1996, 5: 299-314.
Hubbell E, Liu WM, Mei R: Robust estimators for expression analysis. Bioinformatics. 2002, 18: 1585-1592. 10.1093/bioinformatics/18.12.1585.
McGinnis S, Madden TL: BLAST: at the core of a powerful and diverse set of sequence analysis tools. Nucleic Acids Res. 2004, 32: W20-W25. 10.1093/nar/gnh003.
Yuan J, Bush B, Elbrecht A, Liu Y, Zhang T, Zhao W, Blevins R: Enhanced homology searching through genome reading frame predetermination. Bioinformatics. 2004, 20: 1416-1427. 10.1093/bioinformatics/bth115.