Dataset Information

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-literature | 2007

REPOSITORIES: biostudies-literature

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

Messaoudi Lydia L Yang Yun-Gui YG Kinomura Aiko A Stavreva Diana A DA Yan Gonghong G Bortolin-Cavaillé Marie-Line ML Arakawa Hiroshi H Buerstedde Jean-Marie JM Hainaut Pierre P Cavaillé Jérome J Takata Minoru M Van Dyck Eric E

Nucleic acids research 20070928 19

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 ...[more]

PMID: 17905820

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Project description:The present studies aimed to understand the interrelationships between stress, hormones and heat shock proteins (HSPs) in the ovary. We examined (1) whether HSP70.2, HSP72 and HSP105/110 can be produced and accumulated in porcine ovarian tissue, (2) whether these HSPs could be indicators of stress, i.e. whether two kinds of stress (high temperatures and malnutrition/serum deprivation) can affect them, and (3) whether some hormonal regulators of ovarian functions (insulin-like growth factor (IGF)-I, leptin and follicle-stimulating hormone (FSH)) can affect these HSPs and response of ovaries to HSP-related stress. We analysed the expression of HSP70.2, HSP72 and HSP105/110 mRNA (by using real-time reverse transcriptase polymerase chain reaction) in porcine ovarian granulosa cells, as well as the accumulation of HSP70 protein (by using sodium dodecyl sulphate polyacrylamide gel electrophoresis-Western) in either whole ovarian follicles and granulose cells cultured at normal (37.5°C) or high (41.5°C) temperature, with and without serum and with and without IGF-I, leptin and FSH. Expression of mRNA for HSP70.2, HSP72 and HSP105/110 in ovarian granulosa cells and accumulation of HSP70 protein in whole ovarian follicles and granulosa cells were demonstrated. In all the groups, addition of either IGF-I, leptin and FSH reduced the expression of HSP70.2, HSP72 and HSP105/110 mRNA. Both high temperature, serum deprivation and their combination resulted in increase in mRNAs for all three analysed HSPs. Additions of either IGF-I, leptin and FSH prevented the stimulatory effect of both high temperature and serum deprivation on the transcription of HSP70.2, HSP72 and HSP105/110. In contrast, high temperature reduced accumulation of peptide HSP70 in both ovarian follicles and granulosa cell. Serum deprivation promoted accumulation of HSP70 in granulosa cells, but not in ovarian follicles. Addition of IGF-I, leptin and FSH was able to alter accumulation of HSP70 in both follicles and granulosa cells. The present observations suggest (1) that HSPs can be synthesised in ovarian follicular granulosa cells; (2) that hormones (IGF-I, leptin and FSH) can inhibit, whilst stressors (both high temperature and malnutrition/serum deprivation) can stimulate transcription of HSP70.2, HSP72 and HSP105/110 genes, whilst heat stress, but not malnutrition, can promote depletion of HSP70 in ovarian cells, and (3) that hormones (IGF-I, leptin and FSH) can prevent stress-related changes in HSPs. The application of HSPs as indicators and mediators of stress and hormones on ovarian functions, as well as use of hormones and HSPs as anti-stressor molecules, are discussed.

Dataset Information

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

Publications

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

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