Gene isoform

In genetics, gene isoforms are mRNAs that are produced from the same locus but are different in their transcription start sites (TSSs), protein coding DNA sequences (CDSs) and/or untranslated regions (UTRs), potentially altering gene function.

Cis-regulatory elements in the promoter contain sequences recognized by transcription factors and the basal transcription machinery. So the location of the TSS is important for understanding the biogenesis of specific isoforms. The idea that different binding partners confer different functional properties has been well studied in tissue-specific gene regulation.[1] For example, the same transcription factor (TF) can direct gene expression in different tissues simply by binding with different TSSs in each tissue.[2] Isoforms harboring changes in the CDS have been the most thoroughly characterized because they commonly give rise to proteins with different functional properties.[3] UTRs regulate the levels of primary transcript in numerous ways: transcript stability, folding and turnover, as well as translation efficiency. UTRs are often the target of miRNA, which typically downregulate transcript expression by triggering degradation or halting translation.[4]

The gene isoforms can be sequenced by Whole Transcriptome Shotgun Sequencing (RNA-Seq).[4] Recently some progress has been made to characterize known isoforms of regeneration associated genes (RAGs) using RNA-Seq, which is important in understanding the isoform diversity in the CNS.[5][6]

  1. ^ Mitchell PJ, Tjian R (July 1989). "Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins". Science. 245 (4916): 371–8. Bibcode:1989Sci...245..371M. doi:10.1126/science.2667136. PMID 2667136.
  2. ^ Yu X, Lin J, Zack DJ, Qian J (2006). "Computational analysis of tissue-specific combinatorial gene regulation: predicting interaction between transcription factors in human tissues". Nucleic Acids Res. 34 (17): 4925–36. doi:10.1093/nar/gkl595. PMC 1635265. PMID 16982645.
  3. ^ Breitbart RE, Andreadis A, Nadal-Ginard B (1987). "Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes". Annu. Rev. Biochem. 56: 467–95. doi:10.1146/annurev.bi.56.070187.002343. PMID 3304142.
  4. ^ a b van der Velden AW, Thomas AA (January 1999). "The role of the 5' untranslated region of an mRNA in translation regulation during development". Int. J. Biochem. Cell Biol. 31 (1): 87–106. doi:10.1016/S1357-2725(98)00134-4. PMID 10216946.
  5. ^ Wu JQ, Habegger L, Noisa P, Szekely A, Qiu C, Hutchison S, Raha D, Egholm M, Lin H, Weissman S, Cui W, Gerstein M, Snyder M (March 2010). "Dynamic transcriptomes during neural differentiation of human embryonic stem cells revealed by short, long, and paired-end sequencing" (PDF). Proc. Natl. Acad. Sci. U.S.A. 107 (11): 5254–9. Bibcode:2010PNAS..107.5254W. doi:10.1073/pnas.0914114107. PMC 2841935. PMID 20194744.
  6. ^ Barbara Treutlein; Ozgun Gokce; Stephen R. Quake; Thomas C. Südhof (2014). "Cartography of neurexin alternative splicing mapped by single-molecule long-read mRNA sequencing". Proceedings of the National Academy of Sciences of the United States of America. 111 (13): E1291–E1299. Bibcode:2014PNAS..111E1291T. doi:10.1073/pnas.1403244111. PMC 3977267. PMID 24639501.