Geon Alternative RNA Splicing Topics


A gene contains not only the protein-coding regions (exons), but also non-coding regions called introns. After the primary transcript (an RNA) is produced from the DNA that constitutes a gene, introns are removed and exons are joined together, resulting in a messenger RNA (mRNA). This process is known as "RNA splicing". Some exons could be skipped during the splicing process. Since protein synthesis is based on mRNA, different combinations of exons resulting from alternative splicing may express different proteins.

Tau protein plays a central role in Alzheimer's disease and other neurodegenerative disorders. It is encoded by the MAPT gene. Alternative splicing of the MAPT gene generates six Tau isoforms, depending on whether or not the exon 2, 3 or 10 is included (Figure 1). Exons 2 and 3 encode the N-terminal inserts while the exon 10 encodes the second repeat of Tau's microtubule binding domain. A Tau isoform is commonly designated as xNyR, where x is the number of inserts and y is the number of repeats (Figure 2). For instance, 2N4R indicates that it contains two N-terminal inserts and four repeats.


Figure 1. The gene and mRNAs of Tau. In the upper panel, the black boxes represent constitutive exons, and the gray and empty boxes represent alternative spliced exons. The lower panel shows Tau mRNAs in adult human brain. Six mRNAs are generated by alternative splicing of exons 2, 3 and 10, indicated by alternative lines linking these exons. [Source: Liu and Gong, 2008]


Figure 2. Tau isoforms generated by alternative splicing. The longest Tau (2N4R) consists of 441 amino acids while the shortest Tau (0N3R) has 352 amino acids. MTBD: microtubule binding domain. [Source: Guo et al., 2017]


Author: Frank Lee
First published: June 17, 2019