Neurodevelopmental protein Musashi-1 interacts with the Zika genome and promotes viral replication

被引：130

作者：

Chavali, Pavithra L. ^{[1
,8
]}

Stojic, Lovorka ^{[1
]}

Meredith, Luke W. ^{[2
]}

Joseph, Nimesh ^{[1
]}

Nahorski, Michael S. ^{[3
]}

Sanford, Thomas J. ^{[2
]}

Sweeney, Trevor R. ^{[2
]}

Krishna, Ben A. ^{[4
]}

Hosmillo, Myra ^{[2
]}

Firth, Andrew E. ^{[2
]}

Bayliss, Richard ^{[5
]}

Marcelis, Carlo L. ^{[6
]}

Lindsay, Susan ^{[7
]}

Goodfellow, Ian ^{[2
]}

Woods, C. Geoffrey ^{[3
]}

Gergely, Fanni ^{[1
]}

机构：

[1] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Robinson Way, Cambridge CB3 0RE, England

[2] Univ Cambridge, Addenbrookes Hosp, Div Virol, Dept Pathol, Cambridge CB2 2QQ, England

[3] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Hills Rd, Cambridge CB2 0XY, England

[4] Univ Cambridge, Dept Med, Hills Rd, Cambridge CB2 2QQ, England

[5] Univ Leeds, Fac Biol Sci, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England

[6] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, Nijmegen, Netherlands

[7] Newcastle Univ, Inst Med Genet, Int Ctr Life, Cent Pkwy, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England

[8] MRC, Lab Mol Biol, Francis Crick Ave, Cambridge CB2 0QH, England

来源：

SCIENCE | 2017年 / 357卷 / 6346期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

RNA-BINDING PROTEIN; NEURAL PROGENITORS; VIRUS-INFECTION; STEM-CELLS; MOUSE; IDENTIFICATION; MICROCEPHALIN; EXPRESSION; MUTATIONS; BIOLOGY;

D O I：

10.1126/science.aam9243

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

A recent outbreak of Zika virus in Brazil has led to a simultaneous increase in reports of neonatal microcephaly. Zika targets cerebral neural precursors, a cell population essential for cortical development, but the cause of this neurotropism remains obscure. Here we report that the neural RNA-binding protein Musashi-1 (MSI1) interacts with the Zika genome and enables viral replication. Zika infection disrupts the binding of MSI1 to its endogenous targets, thereby deregulating expression of factors implicated in neural stem cell function. We further show that MSI1 is highly expressed in neural progenitors of the human embryonic brain and is mutated in individuals with autosomal recessive primary microcephaly. Selective MSI1 expression in neural precursors could therefore explain the exceptional vulnerability of these cells to Zika infection.

引用

页码：83 / 88

页数：6

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