Interplay Between Pre-mRNA Splicing and MicroRNA Biogenesis Within the Supraspliceosome

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2014 Jan 28

PMID 24464992

Citations 53

Authors

Lily Agranat-Tamir

Noam Shomron

Joseph Sperling

Ruth Sperling

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) are central regulators of gene expression, and a large fraction of them are encoded in introns of RNA polymerase II transcripts. Thus, the biogenesis of intronic miRNAs by the microprocessor and the splicing of their host introns by the spliceosome require coordination between these processing events. This cross-talk is addressed here. We show that key microprocessor proteins Drosha and DGCR8 as well as pre-miRNAs cosediment with supraspliceosomes, where nuclear posttranscriptional processing is executed. We further show that inhibition of splicing increases miRNAs expression, whereas knock-down of Drosha increases splicing. We identified a novel splicing event in intron 13 of MCM7, where the miR-106b-25 cluster is located. The unique splice isoform includes a hosted pre-miRNA in the extended exon and excludes its processing. This indicates a possible mechanism of altering the levels of different miRNAs originating from the same transcript. Altogether, our study indicates interplay between the splicing and microprocessor machineries within a supraspliceosome context.

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References

Smalheiser N . EST analyses predict the existence of a population of chimeric microRNA precursor-mRNA transcripts expressed in normal human and mouse tissues. Genome Biol. 2003; 4(7):403. PMC: 193628. DOI: 10.1186/gb-2003-4-7-403. View

Bernstein E, Caudy A, Hammond S, Hannon G . Role for a bidentate ribonuclease in the initiation step of RNA interference. Nature. 2001; 409(6818):363-6. DOI: 10.1038/35053110. View

Morlando M, Ballarino M, Gromak N, Pagano F, Bozzoni I, Proudfoot N . Primary microRNA transcripts are processed co-transcriptionally. Nat Struct Mol Biol. 2009; 15(9):902-9. PMC: 6952270. DOI: 10.1038/nsmb.1475. View

Petrocca F, Vecchione A, Croce C . Emerging role of miR-106b-25/miR-17-92 clusters in the control of transforming growth factor beta signaling. Cancer Res. 2008; 68(20):8191-4. DOI: 10.1158/0008-5472.CAN-08-1768. View

Landthaler M, Yalcin A, Tuschl T . The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis. Curr Biol. 2004; 14(23):2162-7. DOI: 10.1016/j.cub.2004.11.001. View

Janas M, Khaled M, Schubert S, Bernstein J, Golan D, Veguilla R . Feed-forward microprocessing and splicing activities at a microRNA-containing intron. PLoS Genet. 2011; 7(10):e1002330. PMC: 3197686. DOI: 10.1371/journal.pgen.1002330. View

Rodriguez A, Griffiths-Jones S, Ashurst J, Bradley A . Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004; 14(10A):1902-10. PMC: 524413. DOI: 10.1101/gr.2722704. View

Shen M, Bellaousov S, Hiller M, De La Grange P, Creamer T, Malina O . Pyrvinium pamoate changes alternative splicing of the serotonin receptor 2C by influencing its RNA structure. Nucleic Acids Res. 2013; 41(6):3819-32. PMC: 3616728. DOI: 10.1093/nar/gkt063. View

Azubel M, Wolf S, Sperling J, Sperling R . Three-dimensional structure of the native spliceosome by cryo-electron microscopy. Mol Cell. 2004; 15(5):833-9. DOI: 10.1016/j.molcel.2004.07.022. View

10.

Raitskin O, Cho D, Sperling J, Nishikura K, Sperling R . RNA editing activity is associated with splicing factors in lnRNP particles: The nuclear pre-mRNA processing machinery. Proc Natl Acad Sci U S A. 2001; 98(12):6571-6. PMC: 34394. DOI: 10.1073/pnas.111153798. View

11.

Nicholson P, Yepiskoposyan H, Metze S, Orozco R, Kleinschmidt N, Muhlemann O . Nonsense-mediated mRNA decay in human cells: mechanistic insights, functions beyond quality control and the double-life of NMD factors. Cell Mol Life Sci. 2009; 67(5):677-700. PMC: 11115722. DOI: 10.1007/s00018-009-0177-1. View

12.

Gupta S, Read D, Deepti A, Cawley K, Gupta A, Oommen D . Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis. Cell Death Dis. 2012; 3:e333. PMC: 3388242. DOI: 10.1038/cddis.2012.74. View

13.

Gregory R, Yan K, Amuthan G, Chendrimada T, Doratotaj B, Cooch N . The Microprocessor complex mediates the genesis of microRNAs. Nature. 2004; 432(7014):235-40. DOI: 10.1038/nature03120. View

14.

Azubel M, Habib N, Sperling R, Sperling J . Native spliceosomes assemble with pre-mRNA to form supraspliceosomes. J Mol Biol. 2006; 356(4):955-66. DOI: 10.1016/j.jmb.2005.11.078. View

15.

Miriami E, Angenitzki M, Sperling R, Sperling J . Magnesium cations are required for the association of U small nuclear ribonucleoproteins and SR proteins with pre-mRNA in 200 S large nuclear ribonucleoprotein particles. J Mol Biol. 1995; 246(2):254-63. DOI: 10.1006/jmbi.1994.0081. View

16.

Sperling J, Azubel M, Sperling R . Structure and function of the Pre-mRNA splicing machine. Structure. 2008; 16(11):1605-15. DOI: 10.1016/j.str.2008.08.011. View

17.

Ruby J, Jan C, Bartel D . Intronic microRNA precursors that bypass Drosha processing. Nature. 2007; 448(7149):83-6. PMC: 2475599. DOI: 10.1038/nature05983. View

18.

Knight S, Bass B . A role for the RNase III enzyme DCR-1 in RNA interference and germ line development in Caenorhabditis elegans. Science. 2001; 293(5538):2269-71. PMC: 1855227. DOI: 10.1126/science.1062039. View

19.

Pawlicki J, Steitz J . Nuclear networking fashions pre-messenger RNA and primary microRNA transcripts for function. Trends Cell Biol. 2009; 20(1):52-61. PMC: 2821161. DOI: 10.1016/j.tcb.2009.10.004. View

20.

Fabian M, Sonenberg N . The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol. 2012; 19(6):586-93. DOI: 10.1038/nsmb.2296. View