HnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies

Eun Kyung Lee; Hyeon Ho Kim; Yuki Kuwano; Kotb Abdelmohsen; Subramanya Srikantan; Sarah S. Subaran; Marc Gleichmann; Mohamed R. Mughal; Jennifer L. Martindale; Xiaoling Yang; Paul F. Worley; Mark P. Mattson; Myriam Gorospe

doi:10.1038/nsmb.1815

HnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies

Eun Kyung Lee, Hyeon Ho Kim, Yuki Kuwano, Kotb Abdelmohsen, Subramanya Srikantan, Sarah S. Subaran, Marc Gleichmann, Mohamed R. Mughal, Jennifer L. Martindale, Xiaoling Yang, Paul F. Worley, Mark P. Mattson, Myriam Gorospe

School of Medicine

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

106 Scopus citations

Abstract

Amyloid precursor protein (APP) regulates neuronal synapse function, and its cleavage product AΒ is linked to Alzheimer's disease. Here, we present evidence that the RNA-binding proteins (RBPs) heterogeneous nuclear ribonucleoprotein (hnRNP) C and fragile X mental retardation protein (FMRP) associate with the same APP mRNA coding region element, and they influence APP translation competitively and in opposite directions. Silencing hnRNP C increased FMRP binding to APP mRNA and repressed APP translation, whereas silencing FMRP enhanced hnRNP C binding and promoted translation. Repression of APP translation was linked to colocalization of FMRP and tagged APP RNA within processing bodies; this colocalization was abrogated by hnRNP C overexpression or FMRP silencing. Our findings indicate that FMRP represses translation by recruiting APP mRNA to processing bodies, whereas hnRNP C promotes APP translation by displacing FMRP, thereby relieving the translational block.

Original language	English (US)
Pages (from-to)	732-739
Number of pages	8
Journal	Nature Structural and Molecular Biology
Volume	17
Issue number	6
DOIs	https://doi.org/10.1038/nsmb.1815
State	Published - Jun 2010

ASJC Scopus subject areas

Structural Biology
Molecular Biology

Access to Document

10.1038/nsmb.1815

Cite this

Lee, E. K., Kim, H. H., Kuwano, Y., Abdelmohsen, K., Srikantan, S., Subaran, S. S., Gleichmann, M., Mughal, M. R., Martindale, J. L., Yang, X., Worley, P. F., Mattson, M. P., & Gorospe, M. (2010). HnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies. Nature Structural and Molecular Biology, 17(6), 732-739. https://doi.org/10.1038/nsmb.1815

@article{87ff2a1518334840ace24deb00bfcf3d,

title = "HnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies",

abstract = "Amyloid precursor protein (APP) regulates neuronal synapse function, and its cleavage product AΒ is linked to Alzheimer's disease. Here, we present evidence that the RNA-binding proteins (RBPs) heterogeneous nuclear ribonucleoprotein (hnRNP) C and fragile X mental retardation protein (FMRP) associate with the same APP mRNA coding region element, and they influence APP translation competitively and in opposite directions. Silencing hnRNP C increased FMRP binding to APP mRNA and repressed APP translation, whereas silencing FMRP enhanced hnRNP C binding and promoted translation. Repression of APP translation was linked to colocalization of FMRP and tagged APP RNA within processing bodies; this colocalization was abrogated by hnRNP C overexpression or FMRP silencing. Our findings indicate that FMRP represses translation by recruiting APP mRNA to processing bodies, whereas hnRNP C promotes APP translation by displacing FMRP, thereby relieving the translational block.",

author = "Lee, {Eun Kyung} and Kim, {Hyeon Ho} and Yuki Kuwano and Kotb Abdelmohsen and Subramanya Srikantan and Subaran, {Sarah S.} and Marc Gleichmann and Mughal, {Mohamed R.} and Martindale, {Jennifer L.} and Xiaoling Yang and Worley, {Paul F.} and Mattson, {Mark P.} and Myriam Gorospe",

note = "Funding Information: We thank F.E. Indig and M.H. Dehoff for assistance with experiments. This research was supported by the National Institute on Aging-Intramural Research Program, US National Institutes of Health. P.F.W. is suppported by DA00266.",

year = "2010",

month = jun,

doi = "10.1038/nsmb.1815",

language = "English (US)",

volume = "17",

pages = "732--739",

journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - HnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies

AU - Lee, Eun Kyung

AU - Kim, Hyeon Ho

AU - Kuwano, Yuki

AU - Abdelmohsen, Kotb

AU - Srikantan, Subramanya

AU - Subaran, Sarah S.

AU - Gleichmann, Marc

AU - Mughal, Mohamed R.

AU - Martindale, Jennifer L.

AU - Yang, Xiaoling

AU - Worley, Paul F.

AU - Mattson, Mark P.

AU - Gorospe, Myriam

N1 - Funding Information: We thank F.E. Indig and M.H. Dehoff for assistance with experiments. This research was supported by the National Institute on Aging-Intramural Research Program, US National Institutes of Health. P.F.W. is suppported by DA00266.

PY - 2010/6

Y1 - 2010/6

N2 - Amyloid precursor protein (APP) regulates neuronal synapse function, and its cleavage product AΒ is linked to Alzheimer's disease. Here, we present evidence that the RNA-binding proteins (RBPs) heterogeneous nuclear ribonucleoprotein (hnRNP) C and fragile X mental retardation protein (FMRP) associate with the same APP mRNA coding region element, and they influence APP translation competitively and in opposite directions. Silencing hnRNP C increased FMRP binding to APP mRNA and repressed APP translation, whereas silencing FMRP enhanced hnRNP C binding and promoted translation. Repression of APP translation was linked to colocalization of FMRP and tagged APP RNA within processing bodies; this colocalization was abrogated by hnRNP C overexpression or FMRP silencing. Our findings indicate that FMRP represses translation by recruiting APP mRNA to processing bodies, whereas hnRNP C promotes APP translation by displacing FMRP, thereby relieving the translational block.

AB - Amyloid precursor protein (APP) regulates neuronal synapse function, and its cleavage product AΒ is linked to Alzheimer's disease. Here, we present evidence that the RNA-binding proteins (RBPs) heterogeneous nuclear ribonucleoprotein (hnRNP) C and fragile X mental retardation protein (FMRP) associate with the same APP mRNA coding region element, and they influence APP translation competitively and in opposite directions. Silencing hnRNP C increased FMRP binding to APP mRNA and repressed APP translation, whereas silencing FMRP enhanced hnRNP C binding and promoted translation. Repression of APP translation was linked to colocalization of FMRP and tagged APP RNA within processing bodies; this colocalization was abrogated by hnRNP C overexpression or FMRP silencing. Our findings indicate that FMRP represses translation by recruiting APP mRNA to processing bodies, whereas hnRNP C promotes APP translation by displacing FMRP, thereby relieving the translational block.

UR - http://www.scopus.com/inward/record.url?scp=77953249227&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953249227&partnerID=8YFLogxK

U2 - 10.1038/nsmb.1815

DO - 10.1038/nsmb.1815

M3 - Article

C2 - 20473314

AN - SCOPUS:77953249227

SN - 1545-9993

VL - 17

SP - 732

EP - 739

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 6

ER -

HnRNP C promotes APP translation by competing with FMRP for APP mRNA recruitment to P bodies

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this