Journal
BLOOD
Volume 107, Issue 6, Pages 2557-2561Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2005-07-2957
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Funding
- NIDDK NIH HHS [DK32094, P01 DK032094] Funding Source: Medline
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The human genome uses alternative pre-mRNA splicing as an important mechanism to encode a complex proteome from a relatively small number of genes. An unknown number of these genes also possess multiple transcriational promoters and alternative first exons that contribute another layer of complexity to gene expression mechanisms. Using a collection of more than 100 erythroid-expressed genes as a test group, we used genome browser tools and genetic databases to assess the frequency of alternative first exons in the genome. Remarkably, 35% of these erythroid genes show evidence of alternative first exons. The majority of the candidate first exons are situated upstream of the coding exons, whereas a few are located internally within the gene. Computational analyses predict transcriptional promoters closely associated with many of the candidate first exons, supporting their authenticity. Importantly, the frequent presence of consensus translation initiation sites among the alternative first exons suggests that many proteins have alternative N-terminal structures whose expression can be coupled to promoter choice. These findings indicate that alternative promoters and first exons are more widespread in the human genome than previously appreciated and that they may play a major role in regulating expression of selected protein isoforms in a tissue-specific manner.
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