Open Access

Samoil Sekulovski, Simon Trowitzsch

• Transfer RNAs (tRNAs) are highly structured non-coding RNAs which play key roles in translation and cellular homeostasis. tRNAs are initially transcribed as precursor molecules and mature by tightly controlled, multistep processes that involve the removal of flanking and intervening sequences, over 100 base modifications, addition of non-templated nucleotides and aminoacylation. These molecular events are intertwined with the nucleocy- toplasmic shuttling of tRNAs to make them available at translating ribosomes. Defects in tRNA processing are linked to the development of neurodegenerative disorders. Here, we summarize structural aspects of tRNA processing steps with a special emphasis on intron-containing tRNA splicing involving tRNA splicing endonuclease and ligase. Their role in neurological pathologies will be discussed. Identification of novel RNA substrates of the tRNA splicing machinery has uncovered functions unrelated to tRNA processing. Future structural and biochemical studies will unravel their mechanistic underpinnings and deepen our understanding of neurological diseases.