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| Status |
Public on Nov 06, 2014 |
| Title |
RBBP6 isoforms regulate the human polyadenylation machinery and modulate expression of mRNAs with AU-rich 3' UTRs |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Polyadenylation of mRNA precursors is mediated by a large multisubunit protein complex. Here we show that RBBP6 (retinoblastoma-binding protein 6), identified initially as an Rb- and p53-binding protein, is a component of this complex and functions in 3' processing in vitro and in vivo. RBBP6 associates with other core factors, and this interaction is mediated by an unusual ubiquitin-like domain, DWNN (domain with no name), that is required for 3' processing activity. The DWNN is also expressed, via alternative RNA processing, as a small single-domain protein (isoform 3 [iso3]). Importantly, we show that iso3, known to be down-regulated in several cancers, competes with RBBP6 for binding to the core machinery, thereby inhibiting 3' processing. Genome-wide analyses following RBBP6 knockdown revealed decreased transcript levels, especially of mRNAs with AU-rich 3' untranslated regions (UTRs) such as c-Fos and c-Jun, and increased usage of distal poly(A) sites. Our results implicate RBBP6 and iso3 as novel regulators of 3' processing, especially of RNAs with AU-rich 3' UTRs.
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| Overall design |
RBBP6 siRNA or control siRNA was transfected in MCF7 cells in duplicates and RNA was hybridized to GeneChip Exon 1.0 ST arrays (Affymetrix)
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| Contributor(s) |
DiGiammartino DC, Li W, Ogami K, Yashinskie JJ, Hoque M, Tian B, Manley JL |
| Citation(s) |
25319826 |
| Submission date |
Nov 06, 2014 |
| Last update date |
Nov 06, 2014 |
| Contact name |
Wencheng Li |
| Organization name |
PTC Therapeutics
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| Street address |
100 Corporate Count
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| City |
South Plainfield |
| State/province |
NJ - New Jersey |
| ZIP/Postal code |
07080 |
| Country |
USA |
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| Platforms (1) |
| GPL5188 |
[HuEx-1_0-st] Affymetrix Human Exon 1.0 ST Array [probe set (exon) version] |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA266485 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE63036_RAW.tar |
92.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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