TSEN54

TSEN54

TSEN54 is a gene that encodes a protein component of the tRNA splicing endonuclease complex, which is crucial for the processing of precursor tRNA molecules in eukaryotic cells. This gene is located on chromosome 17 in humans and is involved in the precise cleavage of tRNA precursors to generate mature tRNA molecules necessary for protein synthesis.

Function

The TSEN54 protein is a part of the tRNA splicing endonuclease complex, which also includes TSEN2, TSEN15, and TSEN34. This complex is responsible for the endonucleolytic cleavage of introns from precursor tRNA molecules. The removal of these introns is essential for the proper maturation and function of tRNA, which in turn is critical for the translation of genetic information into proteins.

Clinical Significance

Mutations in the TSEN54 gene have been associated with a group of rare neurodevelopmental disorders known as pontocerebellar hypoplasia (PCH). Specifically, mutations in TSEN54 are linked to Pontocerebellar Hypoplasia Type 2A and Pontocerebellar Hypoplasia Type 4. These conditions are characterized by underdevelopment of the cerebellum and brainstem, leading to severe motor and cognitive impairments.

Pontocerebellar Hypoplasia Type 2A

Pontocerebellar Hypoplasia Type 2A (PCH2A) is a severe neurodegenerative disorder that presents in infancy. It is characterized by progressive microcephaly, profound developmental delay, and early death. The condition is caused by mutations in the TSEN54 gene that disrupt the normal function of the tRNA splicing endonuclease complex.

Pontocerebellar Hypoplasia Type 4

Pontocerebellar Hypoplasia Type 4 (PCH4) is another form of the disorder associated with TSEN54 mutations. It shares many clinical features with PCH2A, including cerebellar hypoplasia and severe developmental delay, but may have distinct neuropathological findings.

Research and Studies

Research into TSEN54 and its associated disorders is ongoing, with studies focusing on understanding the molecular mechanisms by which TSEN54 mutations lead to neurodevelopmental abnormalities. Animal models and cellular studies are used to investigate the role of TSEN54 in brain development and function.

Also see

• tRNA Splicing Endonuclease Complex
• Pontocerebellar Hypoplasia
• TSEN2
• TSEN15
• TSEN34