Multiple domains control the subcellular localization and activity of ETR-3, a regulator of nuclear and cytoplasmic RNA processing events

Journal of Cell Science
Andrea N Ladd, Thomas A Cooper

Abstract

Embryonic lethal abnormal vision (ELAV) type RNA binding protein 3 (ETR-3; also called NAPOR, CUGBP2, or BRUNOL3) has been implicated in the regulation of nuclear and cytoplasmic RNA processing events, including alternative splicing, RNA editing, stability and translation. Here, we report that the ETR-3 protein contains multiple regions that control its subcellular localization and are important for its activity as a splicing regulator. We cloned ETR-3 from chicken heart and fused it to the C terminus of green fluorescent protein (GFPcETR3vL). GFPcETR3vL is found predominantly in the nucleus and is an active regulator of alternative splicing in cotransfection assays with a cardiac troponin T minigene. ETR-3 contains two N-terminal RNA recognition motifs (RRMs), a 210-amino acid divergent domain, and a C-terminal RRM. We demonstrate that the C terminus contains a strong nuclear localization signal overlapping the third RRM, which can confer nuclear localization on a normally cytoplasmic pyruvate kinase chimera. Additional deletions revealed nuclear localization and export activities in the divergent domain of ETR-3, as well as regions within the first two RRMs that are important for cytoplasmic localization. The nuclear export a...Continue Reading

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Citations

Jan 17, 2007·Nature Reviews. Microbiology·Julian A Hiscox
May 17, 2005·Nucleic Acids Research·Jin Han, Thomas A Cooper
Jul 16, 2010·Nucleic Acids Research·Gwendal DujardinLaurent Corcos
Jul 1, 2005·Molecular and Cellular Biology·Andrea N LaddThomas A Cooper
Mar 22, 2012·BMC Biochemistry·Hitoshi SuzukiToshifumi Tsukahara
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Apr 15, 2005·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Andrea N LaddThomas A Cooper
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Jan 26, 2021·Frontiers in Microbiology·Xin Zhao, Suresh K Tikoo

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