Gle1 is a nucleocytoplasmic shuttling protein with well documented cytoplasmic roles as a modulator of ATP-dependent DEAD box RNA helicases involved in messenger (m)RNA export, translation initiation and termination, and stress granule dynamics. Here, we identify a novel nuclear role for Gle1 during transcription termination. In HeLa cells treated with a peptide that disrupts Gle1 nucleocytoplasmic shuttling, we detected nuclear accumulation of specific mRNAs with elongated 3’-UTR. Enriched mRNAs were nascently transcribed and accumulated in the nucleus due to a change in transcription state and not due to altered nuclear export. Whereas Gle1 shuttling inhibition did not appear to perturb nuclear DDX19 functions, it did result in increased DDX1 nucleoplasmic localization and decreased DDX1 interactions with Gle1 and the pre-mRNA cleavage stimulation factor CstF-64. An increase in nuclear R-loop signal intensity was also observed with diminished Gle1 shuttling, as well as colocalization of Gle1 at R-loops. Taken together, these studies reveal a nuclear role for Gle1 in coordinating DDX1 function in transcription termination complexes.

Gle1是一种核质穿梭蛋白，具有充分证明的胞质作用，可作为信使（m）RNA输出，翻译起始和终止以及应激颗粒动力学过程中依赖ATP的DEAD box RNA解旋酶的调节剂。在这里，我们确定转录终止期间Gle1的新型核作用。在用破坏Gle1核质穿梭的肽处理的HeLa细胞中，我们检测到具有延长的3'-UTR的特定mRNA的核积累。由于转录状态的改变而不是由于核输出的改变，富集的mRNA初次转录并积累在细胞核中。尽管Gle1穿梭抑制似乎并未干扰DDX19核功能，它确实导致DDX1核质定位增加，并且DDX1与Gle1和前mRNA裂解刺激因子CstF-64的相互作用降低。还观察到核R环信号强度的增加，同时减少了Gle1穿梭，以及Gle1在R环处的共定位。综上所述，这些研究揭示了Gle1在协调转录终止复合物中DDX1功能中的核作用。