TY - JOUR
T1 - An Architectural Role for a Nuclear Noncoding RNA
T2 - NEAT1 RNA Is Essential for the Structure of Paraspeckles
AU - Clemson, Christine M.
AU - Hutchinson, John N.
AU - Sara, Sergio A.
AU - Ensminger, Alexander W.
AU - Fox, Archa H.
AU - Chess, Andrew
AU - Lawrence, Jeanne B.
N1 - Funding Information:
We wish to thank Chris Lynch, John Butler, Meg Byron, and Agata Sadowska for experimental help and Charles Bond, Daniel Passon, and Mihwa Lee for providing purified recombinant PSP1/p54nrb proteins and intellectual input on nitrocellulose binding assays. This work was supported in part by NIH grants GM53234 and GM68138 to J.B.L., HD007439 fellowship to C.M.C., GM068711 and DC003263 to A.C. and NHMRC grants 402865 and 458751 to A.H.F. and 512880 to S.A.S.
PY - 2009/3/27
Y1 - 2009/3/27
N2 - NEAT1 RNA, a highly abundant 4 kb ncRNA, is retained in nuclei in approximately 10 to 20 large foci that we show are completely coincident with paraspeckles, nuclear domains implicated in mRNA nuclear retention. Depletion of NEAT1 RNA via RNAi eradicates paraspeckles, suggesting that it controls sequestration of the paraspeckle proteins PSP1 and p54, factors linked to A-I editing. Unlike overexpression of PSP1, NEAT1 overexpression increases paraspeckle number, and paraspeckles emanate exclusively from the NEAT1 transcription site. The PSP-1 RNA binding domain is required for its colocalization with NEAT1 RNA in paraspeckles, and biochemical analyses support that NEAT1 RNA binds with paraspeckle proteins. Unlike other nuclear-retained RNAs, NEAT1 RNA is not A-I edited, consistent with a structural role in paraspeckles. Collectively, results demonstrate that NEAT1 functions as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the foundation of a nuclear domain.
AB - NEAT1 RNA, a highly abundant 4 kb ncRNA, is retained in nuclei in approximately 10 to 20 large foci that we show are completely coincident with paraspeckles, nuclear domains implicated in mRNA nuclear retention. Depletion of NEAT1 RNA via RNAi eradicates paraspeckles, suggesting that it controls sequestration of the paraspeckle proteins PSP1 and p54, factors linked to A-I editing. Unlike overexpression of PSP1, NEAT1 overexpression increases paraspeckle number, and paraspeckles emanate exclusively from the NEAT1 transcription site. The PSP-1 RNA binding domain is required for its colocalization with NEAT1 RNA in paraspeckles, and biochemical analyses support that NEAT1 RNA binds with paraspeckle proteins. Unlike other nuclear-retained RNAs, NEAT1 RNA is not A-I edited, consistent with a structural role in paraspeckles. Collectively, results demonstrate that NEAT1 functions as an essential structural determinant of paraspeckles, providing a precedent for a ncRNA as the foundation of a nuclear domain.
KW - RNA
UR - https://www.scopus.com/pages/publications/62549117314
U2 - 10.1016/j.molcel.2009.01.026
DO - 10.1016/j.molcel.2009.01.026
M3 - Article
C2 - 19217333
AN - SCOPUS:62549117314
SN - 1097-2765
VL - 33
SP - 717
EP - 726
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -