The steroid receptor RNA activator gene (SRA1) generates two distinct entities. SRA
RNA coactivates several NRs whereas SRA protein (SRAP) is suspected to regulate
the activity of several transcription factors, including estrogen receptors (ER).
Splicing of SRA intron-1 is the major event defining SRAP coding frame. Fully
spliced, coding SRA and intron-1 retained, non-coding SRA coexist in breast cancer
cells. The relative proportion between the two types of SRA RNA maintains a balance
between two genetically linked entities, SRA and SRAP.
In this study, a minigene model was used to demonstrate that the primary sequence of
SRA exon-1-intron-1-exon-2 is sufficient for alternative splicing of SRA intron-1. In
addition, a modified oligoribonucleotidic construct promotes SRA intron-1 retention
in breast cancer cells. This oligoribonucleotide differentially alters estradiol-induced
transcription of ER regulated genes. Together, results presented herein demonstrate
that the SRA-SRAP balance, which can be artificially modified by targeting
alternative splicing of SRA intron-1, might be a new critical target to treat breast
cancer patients.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:MWU.1993/3097 |
| Date | 26 September 2008 |
| Creators | Guo, Jimin |
| Contributors | Leygue, Etienne (Biochemistry and Medical Genetics), Amara, Francis (Biochemistry and Medical Genetics) Xie, Jiuyong (Physiology) |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_US |
| Detected Language | English |
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