HNS, a nuclear-cytoplasmic shuttling sequence in HuR

HNS, a nuclear-cytoplasmic shuttling sequence in HuR

Howard Hughes Medical Institute, Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, Boyer Center for Molecular Medicine, New Haven, CT 06536

Contributed by Joan A. Steitz

Abstract

Proteins are transported into and out of the cell nucleus via specific signals. The two best-studied nuclear transport processes are mediated either by classical nuclear localization signals or nuclear export signals. There also are shuttling sequences that direct the bidirectional transport of RNA-binding proteins. Two examples are the M9 sequence in heterogeneous nuclear ribonucleoprotein A1 and the heterogeneous nuclear ribonucleoprotein K shuttling domain (KNS) sequence in heterogeneous nuclear ribonucleoprotein K, both of which appear to contribute importantly to the export of mRNA to the cytoplasm. HuR is an RNA-binding protein that can stabilize labile mRNAs containing AU-rich elements in their 3′ untranslated regions and has been shown to shuttle between the nucleus and cytoplasm (18, 19). We have identified in HuR a shuttling sequence that also possess transcription-dependent nuclear localization signal activity. We propose that HuR first may bind AU-rich element-containing mRNAs in the nucleus and then escort them through the nuclear pore, providing protection during and after export to the cytoplasmic compartment.

Footnotes

↵ * Current address: Department of Human Genetics, University of Michigan, Medical Science, Ann Arbor, MI 48109.
↵ † To whom reprint requests should be addressed. e-mail: Joan.Steitz{at}Yale.edu.
ABBREVIATIONS:

NLS,

nuclear localization signal;

NES,

nuclear export signal;

ARE,

AU-rich element;

RRM,

RNA recognition motif;

pol II,

RNA polymerase II;

PK,

pyruvate kinase;

NPc,

nucleoplasmin;

HNS,

HuR nucleocytoplasmic shuttling sequence;

hnRNP,

heterogeneous nuclear ribonucleoprotein