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Regulated splicing of gamma2 pre-messenger RNA in neuronal cells.

Abstract

The pre-mRNA encoding the gamma 2 subunit of the gamma-aminobutyric acid Type A receptor is spliced in a tissue-specific manner in mammalian brain resulting in mRNAs containing or lacking a 24 nucleotide exon, gamma 2L and gamma 2S, respectively. The gamma 2S mRNA predominates in pituitary, whereas the gamma 2L predominates in brainstem, spinal cord and cerebellum. In this study, a cell line derived from rat cerebellum that qualitatively reproduces regulated splicing of gamma 2 pre-mRNA was identified and used to dissect cis-regulatory elements. Sequence elements that alter the selection of the 24 nucleotide exon fall into two functional classes-activating elements and inhibitory elements. We identified several inhibitory elements that inhibit splicing of the 24 nucleotide exon in all cell types as well as specific inhibitory elements which repress splicing in non-neuronal cells. Activating elements are localized within conserved intron regions, as judged by a comparison of rat and human gene sequences, and appear to function generally in activating splicing of the 24 nucleotide exon in the cell types tested so far. These results are compatible with a hypothesis in which the mechanism of regulation involves a release from inhibition. Current experiments are aimed toward the development of tools to identify the trans-regulatory components.

Authors+Show Affiliations

Howard Hughes Medical Institute, University of Pittsburgh, PA 15260, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8643374

Citation

Ashiya, M, et al. "Regulated Splicing of Gamma2 Pre-messenger RNA in Neuronal Cells." Nucleic Acids Symposium Series, 1995, pp. 215-6.
Ashiya M, Zhang L, Grabowski PJ. Regulated splicing of gamma2 pre-messenger RNA in neuronal cells. Nucleic Acids Symp Ser. 1995.
Ashiya, M., Zhang, L., & Grabowski, P. J. (1995). Regulated splicing of gamma2 pre-messenger RNA in neuronal cells. Nucleic Acids Symposium Series, (33), 215-6.
Ashiya M, Zhang L, Grabowski PJ. Regulated Splicing of Gamma2 Pre-messenger RNA in Neuronal Cells. Nucleic Acids Symp Ser. 1995;(33)215-6. PubMed PMID: 8643374.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulated splicing of gamma2 pre-messenger RNA in neuronal cells. AU - Ashiya,M, AU - Zhang,L, AU - Grabowski,P J, PY - 1995/1/1/pubmed PY - 1995/1/1/medline PY - 1995/1/1/entrez SP - 215 EP - 6 JF - Nucleic acids symposium series JO - Nucleic Acids Symp Ser IS - 33 N2 - The pre-mRNA encoding the gamma 2 subunit of the gamma-aminobutyric acid Type A receptor is spliced in a tissue-specific manner in mammalian brain resulting in mRNAs containing or lacking a 24 nucleotide exon, gamma 2L and gamma 2S, respectively. The gamma 2S mRNA predominates in pituitary, whereas the gamma 2L predominates in brainstem, spinal cord and cerebellum. In this study, a cell line derived from rat cerebellum that qualitatively reproduces regulated splicing of gamma 2 pre-mRNA was identified and used to dissect cis-regulatory elements. Sequence elements that alter the selection of the 24 nucleotide exon fall into two functional classes-activating elements and inhibitory elements. We identified several inhibitory elements that inhibit splicing of the 24 nucleotide exon in all cell types as well as specific inhibitory elements which repress splicing in non-neuronal cells. Activating elements are localized within conserved intron regions, as judged by a comparison of rat and human gene sequences, and appear to function generally in activating splicing of the 24 nucleotide exon in the cell types tested so far. These results are compatible with a hypothesis in which the mechanism of regulation involves a release from inhibition. Current experiments are aimed toward the development of tools to identify the trans-regulatory components. SN - 0261-3166 UR - https://www.unboundmedicine.com/medline/citation/8643374/Regulated_splicing_of_gamma2_pre_messenger_RNA_in_neuronal_cells_ DB - PRIME DP - Unbound Medicine ER -