Structure of Human DROSHA

S. Chul Kwon; Tuan Anh Nguyen; Yeon Gil Choi; Myung Hyun Jo; Sungchul Hohng; V. Narry Kim; Jae Sung Woo

doi:10.1016/j.cell.2015.12.019

Structure of Human DROSHA

S. Chul Kwon, Tuan Anh Nguyen, Yeon Gil Choi, Myung Hyun Jo, Sungchul Hohng, V. Narry Kim, Jae Sung Woo

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

162 Citations (Scopus)

Abstract

MicroRNA maturation is initiated by RNase III DROSHA that cleaves the stem loop of primary microRNA. DROSHA functions together with its cofactor DGCR8 in a heterotrimeric complex known as Microprocessor. Here, we report the X-ray structure of DROSHA in complex with the C-terminal helix of DGCR8. We find that DROSHA contains two DGCR8-binding sites, one on each RNase III domain (RIIID), which mediate the assembly of Microprocessor. The overall structure of DROSHA is surprisingly similar to that of Dicer despite no sequence homology apart from the C-terminal part, suggesting that DROSHA may have evolved from a Dicer homolog. DROSHA exhibits unique features, including non-canonical zinc-finger motifs, a long insertion in the first RIIID, and the kinked link between Connector helix and RIIID, which explains the 11-bp-measuring "ruler" activity of DROSHA. Our study implicates the evolutionary origin of DROSHA and elucidates the molecular basis of Microprocessor assembly and primary microRNA processing.

Original language	English
Pages (from-to)	81-90
Number of pages	10
Journal	Cell
Volume	164
Issue number	1-2
DOIs	https://doi.org/10.1016/j.cell.2015.12.019
Publication status	Published - 2016 Jan 14
Externally published	Yes

Bibliographical note

Funding Information:
We thank the beamline staffs at the Pohang Accelerator Laboratory for assistance with data collection. This work was supported by IBS-R008-D1 of Institute for Basic Science from the Ministry of Science, ICT, and Future Planning of Korea (S.C.K., T.A.N., Y.-G.C., J.-S.W., and V.N.K.) and Creative Research Initiatives (2009-0081562) of the National Research Foundation of Korea (M.H.J. and S.H.).

Publisher Copyright:
© 2016 Elsevier Inc.

ASJC Scopus subject areas

General Biochemistry,Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2015.12.019

Cite this

@article{74479802eaeb4e9f84b84d30c5b8f648,

title = "Structure of Human DROSHA",

abstract = "MicroRNA maturation is initiated by RNase III DROSHA that cleaves the stem loop of primary microRNA. DROSHA functions together with its cofactor DGCR8 in a heterotrimeric complex known as Microprocessor. Here, we report the X-ray structure of DROSHA in complex with the C-terminal helix of DGCR8. We find that DROSHA contains two DGCR8-binding sites, one on each RNase III domain (RIIID), which mediate the assembly of Microprocessor. The overall structure of DROSHA is surprisingly similar to that of Dicer despite no sequence homology apart from the C-terminal part, suggesting that DROSHA may have evolved from a Dicer homolog. DROSHA exhibits unique features, including non-canonical zinc-finger motifs, a long insertion in the first RIIID, and the kinked link between Connector helix and RIIID, which explains the 11-bp-measuring {"}ruler{"} activity of DROSHA. Our study implicates the evolutionary origin of DROSHA and elucidates the molecular basis of Microprocessor assembly and primary microRNA processing.",

author = "Kwon, {S. Chul} and Nguyen, {Tuan Anh} and Choi, {Yeon Gil} and Jo, {Myung Hyun} and Sungchul Hohng and Kim, {V. Narry} and Woo, {Jae Sung}",

note = "Funding Information: We thank the beamline staffs at the Pohang Accelerator Laboratory for assistance with data collection. This work was supported by IBS-R008-D1 of Institute for Basic Science from the Ministry of Science, ICT, and Future Planning of Korea (S.C.K., T.A.N., Y.-G.C., J.-S.W., and V.N.K.) and Creative Research Initiatives (2009-0081562) of the National Research Foundation of Korea (M.H.J. and S.H.). Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = jan,

day = "14",

doi = "10.1016/j.cell.2015.12.019",

language = "English",

volume = "164",

pages = "81--90",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "1-2",

}

TY - JOUR

T1 - Structure of Human DROSHA

AU - Kwon, S. Chul

AU - Nguyen, Tuan Anh

AU - Choi, Yeon Gil

AU - Jo, Myung Hyun

AU - Hohng, Sungchul

AU - Kim, V. Narry

AU - Woo, Jae Sung

N1 - Funding Information: We thank the beamline staffs at the Pohang Accelerator Laboratory for assistance with data collection. This work was supported by IBS-R008-D1 of Institute for Basic Science from the Ministry of Science, ICT, and Future Planning of Korea (S.C.K., T.A.N., Y.-G.C., J.-S.W., and V.N.K.) and Creative Research Initiatives (2009-0081562) of the National Research Foundation of Korea (M.H.J. and S.H.). Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/1/14

Y1 - 2016/1/14

N2 - MicroRNA maturation is initiated by RNase III DROSHA that cleaves the stem loop of primary microRNA. DROSHA functions together with its cofactor DGCR8 in a heterotrimeric complex known as Microprocessor. Here, we report the X-ray structure of DROSHA in complex with the C-terminal helix of DGCR8. We find that DROSHA contains two DGCR8-binding sites, one on each RNase III domain (RIIID), which mediate the assembly of Microprocessor. The overall structure of DROSHA is surprisingly similar to that of Dicer despite no sequence homology apart from the C-terminal part, suggesting that DROSHA may have evolved from a Dicer homolog. DROSHA exhibits unique features, including non-canonical zinc-finger motifs, a long insertion in the first RIIID, and the kinked link between Connector helix and RIIID, which explains the 11-bp-measuring "ruler" activity of DROSHA. Our study implicates the evolutionary origin of DROSHA and elucidates the molecular basis of Microprocessor assembly and primary microRNA processing.

AB - MicroRNA maturation is initiated by RNase III DROSHA that cleaves the stem loop of primary microRNA. DROSHA functions together with its cofactor DGCR8 in a heterotrimeric complex known as Microprocessor. Here, we report the X-ray structure of DROSHA in complex with the C-terminal helix of DGCR8. We find that DROSHA contains two DGCR8-binding sites, one on each RNase III domain (RIIID), which mediate the assembly of Microprocessor. The overall structure of DROSHA is surprisingly similar to that of Dicer despite no sequence homology apart from the C-terminal part, suggesting that DROSHA may have evolved from a Dicer homolog. DROSHA exhibits unique features, including non-canonical zinc-finger motifs, a long insertion in the first RIIID, and the kinked link between Connector helix and RIIID, which explains the 11-bp-measuring "ruler" activity of DROSHA. Our study implicates the evolutionary origin of DROSHA and elucidates the molecular basis of Microprocessor assembly and primary microRNA processing.

UR - http://www.scopus.com/inward/record.url?scp=84954392659&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2015.12.019

DO - 10.1016/j.cell.2015.12.019

M3 - Article

C2 - 26748718

AN - SCOPUS:84954392659

SN - 0092-8674

VL - 164

SP - 81

EP - 90

JO - Cell

JF - Cell

IS - 1-2

ER -

Structure of Human DROSHA

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this