RRP44

Rrp44, also known as Dis3, is the catalytic subunit of the RNA exosome, a conserved multi-subunit complex that degrades and processes RNA in eukaryotic cells. In eukaryotes it partners with the exosome core to perform 3' to 5' exonuclease activity, and it can also provide endoribonucleolytic activity via its N-terminal PIN domain under certain conditions.

Structure and mechanism: Rrp44 contains an N-terminal PIN domain responsible for endonucleolytic cleavage, a central RNB (RNase II-like) domain that executes 3' to 5' exonuclease activity, and a C-terminal S1 RNA-binding domain that aids substrate recognition. The catalytic activity is integrated with the exosome core, producing a channel for RNA to reach the nuclease.

Function: The enzyme participates in RNA surveillance and processing, including degradation of defective ribosomal RNA precursors, aberrant snoRNA and mRNA transcripts, and various noncoding RNAs. Through its association with the exosome core and, in some contexts, with Rrp6 in the nucleus, Rrp44 helps regulate RNA quality and turnover in both nuclear and cytoplasmic compartments.

Biological and clinical relevance: Rrp44/Dis3 is essential for viability in many organisms and is highly conserved. In humans, DIS3 and DIS3L are paralogs with overlapping but distinct localizations and substrates; mutations or dysregulation of DIS3 have been linked to hematological malignancies such as multiple myeloma, underscoring the importance of proper exosome function.

Evolution and distribution: Dis3 homologs are found in archaea and eukaryotes as part of the exosome family, reflecting a conserved mechanism of RNA processing and decay.