Transcriptome-wide MiR-155 Binding Map Reveals Widespread Noncanonical MicroRNA Targeting

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Nov 13

PMID 23142080

Citations 215

Authors

Gabriel B Loeb

Aly A Khan

David Canner

Joseph B Hiatt

Jay Shendure

Robert B Darnell

Christina S Leslie

Alexander Y Rudensky

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRNAs) are essential components of gene regulation, but identification of miRNA targets remains a major challenge. Most target prediction and discovery relies on perfect complementarity of the miRNA seed to the 3' untranslated region (UTR). However, it is unclear to what extent miRNAs target sites without seed matches. Here, we performed a transcriptome-wide identification of the endogenous targets of a single miRNA-miR-155-in a genetically controlled manner. We found that approximately 40% of miR-155-dependent Argonaute binding occurs at sites without perfect seed matches. The majority of these noncanonical sites feature extensive complementarity to the miRNA seed with one mismatch. These noncanonical sites confer regulation of gene expression, albeit less potently than canonical sites. Thus, noncanonical miRNA binding sites are widespread, often contain seed-like motifs, and can regulate gene expression, generating a continuum of targeting and regulation.

Citing Articles

Expanding the immune-related targetome of miR-155-5p by integrating time-resolved RNA patterns into miRNA target prediction.

Hart M, Diener C, Rheinheimer S, Kehl T, Keller A, Lenhof H RNA Biol. 2025; 22(1):1-9.

PMID: 39760255 PMC: 11730359. DOI: 10.1080/15476286.2025.2449775.

High-Throughput Quantification of miRNA-3'-Untranslated-Region Regulatory Effects.

Mastriano S, Kanoria S, Rennie W, Liu C, Li D, Cheng J bioRxiv. 2024; .

PMID: 39677669 PMC: 11643113. DOI: 10.1101/2024.12.05.626985.

Advancing microRNA target site prediction with transformer and base-pairing patterns.

Bi Y, Li F, Wang C, Pan T, Davidovich C, Webb G Nucleic Acids Res. 2024; 52(19):11455-11465.

PMID: 39271121 PMC: 11514461. DOI: 10.1093/nar/gkae782.

Genome-wide and cell-type-selective profiling of in vivo small noncoding RNA:target RNA interactions by chimeric RNA sequencing.

Li X, Mills 4th W, Jin D, Meffert M Cell Rep Methods. 2024; 4(8):100836.

PMID: 39127045 PMC: 11384083. DOI: 10.1016/j.crmeth.2024.100836.

BTLA biology in cancer: from bench discoveries to clinical potentials.

Andrzejczak A, Karabon L Biomark Res. 2024; 12(1):8.

PMID: 38233898 PMC: 10795259. DOI: 10.1186/s40364-024-00556-2.

References

Lim L, Lau N, Garrett-Engele P, Grimson A, Schelter J, Castle J . Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature. 2005; 433(7027):769-73. DOI: 10.1038/nature03315. View

Forman J, Legesse-Miller A, Coller H . A search for conserved sequences in coding regions reveals that the let-7 microRNA targets Dicer within its coding sequence. Proc Natl Acad Sci U S A. 2008; 105(39):14879-84. PMC: 2567461. DOI: 10.1073/pnas.0803230105. View

Gottwein E, Corcoran D, Mukherjee N, Skalsky R, Hafner M, Nusbaum J . Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines. Cell Host Microbe. 2011; 10(5):515-26. PMC: 3222872. DOI: 10.1016/j.chom.2011.09.012. View

Ender C, Krek A, Friedlander M, Beitzinger M, Weinmann L, Chen W . A human snoRNA with microRNA-like functions. Mol Cell. 2008; 32(4):519-28. DOI: 10.1016/j.molcel.2008.10.017. View

Lewis B, Burge C, Bartel D . Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell. 2005; 120(1):15-20. DOI: 10.1016/j.cell.2004.12.035. View

Metzler M, Wilda M, Busch K, Viehmann S, Borkhardt A . High expression of precursor microRNA-155/BIC RNA in children with Burkitt lymphoma. Genes Chromosomes Cancer. 2003; 39(2):167-9. DOI: 10.1002/gcc.10316. View

OCarroll D, Mecklenbrauker I, Das P, Santana A, Koenig U, Enright A . A Slicer-independent role for Argonaute 2 in hematopoiesis and the microRNA pathway. Genes Dev. 2007; 21(16):1999-2004. PMC: 1948855. DOI: 10.1101/gad.1565607. View

Mu P, Han Y, Betel D, Yao E, Squatrito M, Ogrodowski P . Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced B-cell lymphomas. Genes Dev. 2009; 23(24):2806-11. PMC: 2800095. DOI: 10.1101/gad.1872909. View

Tay Y, Kats L, Salmena L, Weiss D, Tan S, Ala U . Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 2011; 147(2):344-57. PMC: 3235920. DOI: 10.1016/j.cell.2011.09.029. View

10.

Vigorito E, Perks K, Abreu-Goodger C, Bunting S, Xiang Z, Kohlhaas S . microRNA-155 regulates the generation of immunoglobulin class-switched plasma cells. Immunity. 2007; 27(6):847-59. PMC: 4135426. DOI: 10.1016/j.immuni.2007.10.009. View

11.

Costinean S, Sandhu S, Pedersen I, Tili E, Trotta R, Perrotti D . Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic mice. Blood. 2009; 114(7):1374-82. PMC: 2727407. DOI: 10.1182/blood-2009-05-220814. View

12.

Eis P, Tam W, Sun L, Chadburn A, Li Z, Gomez M . Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc Natl Acad Sci U S A. 2005; 102(10):3627-32. PMC: 552785. DOI: 10.1073/pnas.0500613102. View

13.

Skalsky R, Corcoran D, Gottwein E, Frank C, Kang D, Hafner M . The viral and cellular microRNA targetome in lymphoblastoid cell lines. PLoS Pathog. 2012; 8(1):e1002484. PMC: 3266933. DOI: 10.1371/journal.ppat.1002484. View

14.

Lu L, Boldin M, Chaudhry A, Lin L, Taganov K, Hanada T . Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell. 2010; 142(6):914-29. PMC: 3049116. DOI: 10.1016/j.cell.2010.08.012. View

15.

Schnall-Levin M, Rissland O, Johnston W, Perrimon N, Bartel D, Berger B . Unusually effective microRNA targeting within repeat-rich coding regions of mammalian mRNAs. Genome Res. 2011; 21(9):1395-403. PMC: 3166825. DOI: 10.1101/gr.121210.111. View

16.

Grimson A, Farh K, Johnston W, Garrett-Engele P, Lim L, Bartel D . MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell. 2007; 27(1):91-105. PMC: 3800283. DOI: 10.1016/j.molcel.2007.06.017. View

17.

Poliseno L, Salmena L, Zhang J, Carver B, Haveman W, Pandolfi P . A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature. 2010; 465(7301):1033-8. PMC: 3206313. DOI: 10.1038/nature09144. View

18.

Chi S, Zang J, Mele A, Darnell R . Argonaute HITS-CLIP decodes microRNA-mRNA interaction maps. Nature. 2009; 460(7254):479-86. PMC: 2733940. DOI: 10.1038/nature08170. View

19.

Wang H, Yu X, Liu Z, Cheng X, Samartzis D, Jia L . Deregulated miR-155 promotes Fas-mediated apoptosis in human intervertebral disc degeneration by targeting FADD and caspase-3. J Pathol. 2011; 225(2):232-42. DOI: 10.1002/path.2931. View

20.

Thai T, Calado D, Casola S, Ansel K, Xiao C, Xue Y . Regulation of the germinal center response by microRNA-155. Science. 2007; 316(5824):604-8. DOI: 10.1126/science.1141229. View