An alternative mode of microRNA target recognition

Sung Wook Chi; Gregory J. Hannon; Robert B. Darnell

doi:10.1038/nsmb.2230

An alternative mode of microRNA target recognition

Sung Wook Chi, Gregory J. Hannon, Robert B. Darnell

Research output: Contribution to journal › Article › peer-review

275 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing and analysis of clusters of ∼50-nucleotide mRNA tags cross-linked to Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP 'orphan clusters'-Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches-we have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise ≥15% of all Ago-miRNA interactions in mouse brain and are evolutionarily conserved. We call position 6 the 'pivot' nucleotide and suggest a model in which a transitional 'nucleation bulge' leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites.

Original language	English
Pages (from-to)	321-327
Number of pages	7
Journal	Nature Structural and Molecular Biology
Volume	19
Issue number	3
DOIs	https://doi.org/10.1038/nsmb.2230
Publication status	Published - 2012 Mar
Externally published	Yes

ASJC Scopus subject areas

Structural Biology
Molecular Biology

Access to Document

10.1038/nsmb.2230

Cite this

@article{14d369c194c44c4a91765508c710b8a8,

title = "An alternative mode of microRNA target recognition",

abstract = "MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing and analysis of clusters of ∼50-nucleotide mRNA tags cross-linked to Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP 'orphan clusters'-Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches-we have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise ≥15% of all Ago-miRNA interactions in mouse brain and are evolutionarily conserved. We call position 6 the 'pivot' nucleotide and suggest a model in which a transitional 'nucleation bulge' leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites.",

author = "Chi, {Sung Wook} and Hannon, {Gregory J.} and Darnell, {Robert B.}",

note = "Funding Information: We thank the members of the Darnell and Hannon laboratories for helpful discussions. This work was supported in part by grants from the US National Institutes of Health (R.B.D. and G.J.H.) and a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare (A111989, to S.W.C.). R.B.D. and G.J.H. are investigators of the Howard Hughes Medical Institute.",

year = "2012",

month = mar,

doi = "10.1038/nsmb.2230",

language = "English",

volume = "19",

pages = "321--327",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "Nature Publishing Group",

number = "3",

}

TY - JOUR

T1 - An alternative mode of microRNA target recognition

AU - Chi, Sung Wook

AU - Hannon, Gregory J.

AU - Darnell, Robert B.

N1 - Funding Information: We thank the members of the Darnell and Hannon laboratories for helpful discussions. This work was supported in part by grants from the US National Institutes of Health (R.B.D. and G.J.H.) and a grant from the Korean Health Technology R&D Project, Ministry of Health & Welfare (A111989, to S.W.C.). R.B.D. and G.J.H. are investigators of the Howard Hughes Medical Institute.

PY - 2012/3

Y1 - 2012/3

N2 - MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing and analysis of clusters of ∼50-nucleotide mRNA tags cross-linked to Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP 'orphan clusters'-Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches-we have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise ≥15% of all Ago-miRNA interactions in mouse brain and are evolutionarily conserved. We call position 6 the 'pivot' nucleotide and suggest a model in which a transitional 'nucleation bulge' leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites.

AB - MicroRNAs (miRNAs) regulate mRNA targets through perfect pairing with their seed region (positions 2-7). Recently, a precise genome-wide map of miRNA interaction sites in mouse brain was generated by high-throughput sequencing and analysis of clusters of ∼50-nucleotide mRNA tags cross-linked to Argonaute (Ago HITS-CLIP). By analyzing Ago HITS-CLIP 'orphan clusters'-Ago binding regions from HITS-CLIP that cannot be explained by canonical seed matches-we have now identified an alternative binding mode used by miRNAs. Specifically, G-bulge sites (positions 5-6) are often bound and regulated by miR-124 in brain. More generally, bulged sites comprise ≥15% of all Ago-miRNA interactions in mouse brain and are evolutionarily conserved. We call position 6 the 'pivot' nucleotide and suggest a model in which a transitional 'nucleation bulge' leads to functional bulge mRNA-miRNA interactions, expanding the number of potential miRNA regulatory sites.

UR - http://www.scopus.com/inward/record.url?scp=84857955708&partnerID=8YFLogxK

U2 - 10.1038/nsmb.2230

DO - 10.1038/nsmb.2230

M3 - Article

C2 - 22343717

AN - SCOPUS:84857955708

SN - 1545-9993

VL - 19

SP - 321

EP - 327

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 3

ER -

An alternative mode of microRNA target recognition

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this