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A cytosine-rich splice regulatory determinant enforces functional processing of the human α-globin gene transcript
| Content Provider | Scilit |
|---|---|
| Author | Ji, Xinjun Humenik, Jesse Liebhaber, Stephen A. |
| Copyright Year | 2019 |
| Description | The establishment of efficient and stable splicing patterns in terminally differentiated cells is critical to maintenance of specific functions throughout the lifespan of an organism. The human α-globin (hα-globin) gene contains 3 exons separated by 2 short introns. Naturally occurring α-thalassemia mutations that trigger aberrant splicing have revealed the presence of cryptic splice sites within the hα-globin gene transcript. How cognate (functional) splice sites are selectively used in lieu of these cryptic sites has remained unexplored. Here we demonstrate that the preferential selection of a cognate splice donor essential to functional splicing of the hα-globin transcript is dependent on the actions of an intronic cytosine (C)-rich splice regulatory determinant and its interacting polyC-binding proteins. Inactivation of this determinant by mutation of the C-rich element or by depletion of polyC-binding proteins triggers a dramatic shift in splice donor activity to an upstream, out-of-frame, cryptic donor. The essential role of the C-rich element in hα-globin gene expression is supported by its coevolution with the cryptic donor site in primate species. These data lead us to conclude that an intronic C-rich determinant enforces functional splicing of the hα-globin transcript, thus acting as an obligate determinant of hα-globin gene expression. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533601/pdf |
| Ending Page | 2347 |
| Page Count | 10 |
| Starting Page | 2338 |
| DOI | 10.1182/blood-2018-12-891408 |
| Journal | Blood |
| Issue Number | 21 |
| Volume Number | 133 |
| Language | English |
| Publisher | American Society of Hematology |
| Publisher Date | 2019-05-23 |
| Access Restriction | Open |
| Subject Keyword | Biochemistry and Molecular Biology Gene Expression Evolution Proteins Functional Rich Differentiated Splice Globin Gene Intronic Journal: Blood (Vol- 134, Issue- 21) |
| Content Type | Text |
| Resource Type | Article |
