Unknown

Dataset Information

0

Subcellular distribution of human RDM1 protein isoforms and their nucleolar accumulation in response to heat shock and proteotoxic stress.


ABSTRACT: The RDM1 gene encodes a RNA recognition motif (RRM)-containing protein involved in the cellular response to the anti-cancer drug cisplatin in vertebrates. We previously reported a cDNA encoding the full-length human RDM1 protein. Here, we describe the identification of 11 human cDNAs encoding RDM1 protein isoforms. This repertoire is generated by alternative pre-mRNA splicing and differential usage of two translational start sites, resulting in proteins with long or short N-terminus and a great diversity in the exonic composition of their C-terminus. By using tagged proteins and fluorescent microscopy, we examined the subcellular distribution of full-length RDM1 (renamed RDM1alpha), and other RDM1 isoforms. We show that RDM1alpha undergoes subcellular redistribution and nucleolar accumulation in response to proteotoxic stress and mild heat shock. In unstressed cells, the long N-terminal isoforms displayed distinct subcellular distribution patterns, ranging from a predominantly cytoplasmic to almost exclusive nuclear localization, suggesting functional differences among the RDM1 proteins. However, all isoforms underwent stress-induced nucleolar accumulation. We identified nuclear and nucleolar localization determinants as well as domains conferring cytoplasmic retention to the RDM1 proteins. Finally, RDM1 null chicken DT40 cells displayed an increased sensitivity to heat shock, compared to wild-type (wt) cells, suggesting a function for RDM1 in the heat-shock response.

SUBMITTER: Messaoudi L 

PROVIDER: S-EPMC2095821 | BioStudies | 2007-01-01

REPOSITORIES: biostudies

Similar Datasets

2015-01-01 | S-EPMC4558571 | BioStudies
1000-01-01 | S-EPMC2796889 | BioStudies
2020-01-01 | S-EPMC7652795 | BioStudies
2011-01-01 | S-EPMC3139624 | BioStudies
2015-01-01 | S-EPMC6707813 | BioStudies
2007-01-01 | S-EPMC1896285 | BioStudies
1000-01-01 | S-EPMC2998510 | BioStudies
1000-01-01 | S-EPMC1636418 | BioStudies
2007-01-01 | S-EPMC1876774 | BioStudies
2014-01-01 | S-EPMC4106310 | BioStudies