A structural map of oncomiR-1 at single-nucleotide resolution

Chakraborty, Saikat; Krishnan, Yamuna

doi:10.1093/nar/gkx613

A structural map of oncomiR-1 at single-nucleotide resolution

Journal Article · Mon Jul 17 04:00:00 EDT 2017 · Nucleic Acids Research

DOI:https://doi.org/10.1093/nar/gkx613· OSTI ID:1399130

^[1]; Krishnan, Yamuna ^[2]

National Centre for Biological Sciences (India)
Univ. of Chicago, IL (United States)

The miR-17–92a cluster, also known as ‘oncomiR-1’, is an RNA transcript that plays a pivotal regulatory role in cellular processes, including the cell cycle, proliferation and apoptosis. Its dysregulation underlies the development of several cancers. Oncomir-1 comprises six constituent miRNAs, each processed with different efficiencies as a function of both developmental time and tissue type. The structural mechanisms that regulate such differential processing are unknown, and this has impeded our understanding of the dysregulation of oncomiR-1 in pathophysiology. By probing the sensitivity of each nucleotide in oncomiR-1 to reactive small molecules, we present a secondary structural map of this RNA at single-nucleotide resolution. The secondary structure and solvent accessible regions of oncomiR-1 reveal that most of its primary microRNA domains are suboptimal substrates for Drosha-DGCR8, and therefore resistant to microprocessing. The structure indicates that the binding of trans-acting factors is required to remodel the tertiary organization and unmask cryptic primary microRNA domains to facilitate their processing into pre-microRNAs.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC)

OSTI ID:: 1399130

Journal Information:: Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 16 Vol. 45; ISSN 0305-1048

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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