Tags

Type your tag names separated by a space and hit enter

Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export.
Genes Dev. 1999 Aug 01; 13(15):1994-2004.GD

Abstract

Npl3p, the major mRNA-binding protein of the yeast Saccharomyces cerevisiae shuttles between the nucleus and the cytoplasm. A single amino acid change in the carboxyl terminus of Npl3p (E409 --> K) renders the mutant protein largely cytoplasmic because of a delay in its import into the nucleus. This import defect can be reversed by increasing the intracellular concentration of Mtr10p, the nuclear import receptor for Npl3p. Conversely, using this mutant, we show that Npl3p and mRNA export out of the nucleus is significantly slowed in cells bearing mutations in XPO1/CRM1, which encodes the export receptor for NES-containing proteins and in RAT7, which encodes an essential nucleoporin. Interestingly, following induction of stress by heat shock, high salt, or ethanol, conditions under which most mRNA export is blocked, Npl3p is still exported from the nucleus. The stress-induced export of Npl3p is independent of both the activity of Xpo1p and the continued selective export of heat-shock mRNAs that occurs following stress. UV-cross-linking experiments show that Npl3p is bound to mRNA under normal conditions, but is no longer RNA associated in stressed cells. Taken together, we suggest that the uncoupling of Npl3p and possibly other mRNA-binding proteins from mRNAs in the nucleus provides a general switch that regulates mRNA export. By this model, under normal conditions Npl3p is a major component of an export-competent RNP complex. However, under conditions of stress, Npl3p no longer associates with the export complex, rendering it export incompetent and thus nuclear.

Authors+Show Affiliations

Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and The Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10444597

Citation

Krebber, H, et al. "Uncoupling of the hnRNP Npl3p From mRNAs During the Stress-induced Block in mRNA Export." Genes & Development, vol. 13, no. 15, 1999, pp. 1994-2004.
Krebber H, Taura T, Lee MS, et al. Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export. Genes Dev. 1999;13(15):1994-2004.
Krebber, H., Taura, T., Lee, M. S., & Silver, P. A. (1999). Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export. Genes & Development, 13(15), 1994-2004.
Krebber H, et al. Uncoupling of the hnRNP Npl3p From mRNAs During the Stress-induced Block in mRNA Export. Genes Dev. 1999 Aug 1;13(15):1994-2004. PubMed PMID: 10444597.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Uncoupling of the hnRNP Npl3p from mRNAs during the stress-induced block in mRNA export. AU - Krebber,H, AU - Taura,T, AU - Lee,M S, AU - Silver,P A, PY - 1999/8/13/pubmed PY - 1999/8/13/medline PY - 1999/8/13/entrez SP - 1994 EP - 2004 JF - Genes & development JO - Genes Dev VL - 13 IS - 15 N2 - Npl3p, the major mRNA-binding protein of the yeast Saccharomyces cerevisiae shuttles between the nucleus and the cytoplasm. A single amino acid change in the carboxyl terminus of Npl3p (E409 --> K) renders the mutant protein largely cytoplasmic because of a delay in its import into the nucleus. This import defect can be reversed by increasing the intracellular concentration of Mtr10p, the nuclear import receptor for Npl3p. Conversely, using this mutant, we show that Npl3p and mRNA export out of the nucleus is significantly slowed in cells bearing mutations in XPO1/CRM1, which encodes the export receptor for NES-containing proteins and in RAT7, which encodes an essential nucleoporin. Interestingly, following induction of stress by heat shock, high salt, or ethanol, conditions under which most mRNA export is blocked, Npl3p is still exported from the nucleus. The stress-induced export of Npl3p is independent of both the activity of Xpo1p and the continued selective export of heat-shock mRNAs that occurs following stress. UV-cross-linking experiments show that Npl3p is bound to mRNA under normal conditions, but is no longer RNA associated in stressed cells. Taken together, we suggest that the uncoupling of Npl3p and possibly other mRNA-binding proteins from mRNAs in the nucleus provides a general switch that regulates mRNA export. By this model, under normal conditions Npl3p is a major component of an export-competent RNP complex. However, under conditions of stress, Npl3p no longer associates with the export complex, rendering it export incompetent and thus nuclear. SN - 0890-9369 UR - https://www.unboundmedicine.com/medline/citation/10444597/Uncoupling_of_the_hnRNP_Npl3p_from_mRNAs_during_the_stress_induced_block_in_mRNA_export_ L2 - http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=10444597 DB - PRIME DP - Unbound Medicine ER -