TSEN2

The TSEN2 gene provides instructions for making one part (subunit) of an enzyme called the tRNA splicing endonuclease complex. This complex helps process several types of RNA molecules, which are chemical cousins of DNA.

The tRNA splicing endonuclease complex is particularly important for the normal processing of a form of RNA known as transfer RNA (tRNA). tRNA molecules help assemble protein building blocks known as amino acids into full-length proteins. However, before they can assemble proteins, tRNAs must be processed into mature molecules. In particular, some tRNA molecules contain regions called introns that need to be removed for the tRNAs to be functional. The tRNA splicing endonuclease complex recognizes and then removes introns to help produce mature tRNA molecules.

Studies suggest that the tRNA splicing endonuclease complex may also be involved in processing another form of RNA known as messenger RNA (mRNA). mRNA serves as a genetic blueprint for making proteins. Researchers suspect that the tRNA splicing endonuclease complex cuts (cleaves) one end of mRNA molecules so a string of adenines (one of the building blocks of RNA) can be added. This process is known as polyadenylation, and the string of adenines is known as a poly(A) tail. The poly(A) tail signals the stopping point for protein production and protects mRNA from being broken down before protein production occurs.

pontocerebellar hypoplasia - caused by mutations in the TSEN2 gene

At least one mutation in the TSEN2 gene has been found to cause pontocerebellar hypoplasia type 2 (PCH2). This mutation replaces the amino acid tyrosine with the amino acid cysteine at position 309 in the TSEN2 protein (written as Tyr309Cys or Y309C). It is unclear how mutations in this gene alter the function of the tRNA splicing endonuclease complex and disrupt normal brain development. Researchers believe that TSEN2 gene mutations are probably responsible for only a small percentage of all cases of PCH2.