Translin facilitates RNA polymerase II dissociation and suppresses genome instability during RNase H2- and Dicer-deficiency (data files)

The conserved nucleic acid binding protein Translin contributes to
numerous facets of mammalian biology and genetic diseases. It was first
identified as a binder of cancer-associated chromosomal translocation
breakpoint junctions leading to the suggestion that it was involved in
genetic recombination. With a paralogous partner protein, Trax, Translin
has subsequently been found to form a hetero-octomeric RNase complex that
drives some of its functions, including passenger strand removal in RNA
interference (RNAi).  The Translin-Trax complex also degrades the
precursors to tumour suppressing microRNAs in cancers deficient for the
RNase III Dicer. This oncogenic activity has resulted in the Translin-Trax
complex being explored as a therapeutic target. Additionally, Translin and
Trax have been implicated a wider range of biological function ranging
from sleep regulation to telomere transcript control. Here we reveal a
Trax- and RNAi-independent function for Translin in dissociating RNA
polymerase II from its genomic template, with loss of Translin function
resulting in increased transcription-associated recombination and elevated
genome instability. This provides genetic insight into the longstanding
question of how Translin might influence chromosomal rearrangements in
human genetic diseases and provides important functional understanding of
an oncological therapeutic target.