Ashwin and FAM98 paralogs define nuclear and cytoplasmic RNA ligase complexes for tRNA biogenesis.

Ashwin (ASW) directs nuclear localization of tRNA ligase complex, with FAM98 paralogs determining its cytoplasmic or nuclear form, crucial for tRNA and mRNA splicing.

• Why it matters: Understanding how tRNA ligase complexes are compartmentalized is vital for insights into RNA processing and cellular stress responses, yet the mechanisms controlling their localization remain unclear.
• What they did: The study identified ASW as a vertebrate-specific nuclear import factor with dual NLS signals, and showed that its interaction with FAM98B directs the complex to the nucleus, while other FAM98 paralogs influence cytoplasmic retention.
• The result: Disrupting ASW's NLS impairs pre-tRNA splicing, leading to tRNA fragment accumulation, and attaching an NLS to RTCB restores splicing, highlighting the importance of ASW and FAM98 paralogs in RNA processing compartmentalization.