Circular RNAs (circRNAs), which are increasingly being implicated in a variety of functions in normal and cancerous cells1–5, are formed by back-splicing of precursor mRNAs in the nucleus6–10. circRNAs are predominantly localized in the cytoplasm, indicating that they must be exported from the nucleus. Here we identify a pathway that is specific for the nuclear export of circular RNA. This pathway requires Ran-GTP, exportin-2 and IGF2BP1. Enhancing the nuclear Ran-GTP gradient by depletion or chemical inhibition of the major protein exporter CRM1 selectively increases the nuclear export of circRNAs, while reducing the nuclear Ran-GTP gradient selectively blocks circRNA export. Depletion or knockout of exportin-2 specifically inhibits nuclear export of circRNA. Analysis of nuclear circRNA-binding proteins reveals that interaction between IGF2BP1 and circRNA is enhanced by Ran-GTP. The formation of circRNA export complexes in the nucleus is promoted by Ran-GTP through its int
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Penicillium oxalicum engineered strain DB2 and its mutant strains with multiple regulatory modules were constructed. Mutant strain RE-4-2 with two regulatory modules showed a significant increase in the reducing sugar released from corn stover and corn fiber as well as in the conversion of cellulose than DB2. RE-5-2 with three regulatory modules showed a further increase in reducing sugar released from corn stover and the conversion of cellulose on the basis of RE-4-2. RE-4-2-AraRA731V constructed by overexpressing AraRA731V in RE-4-2 showed an increase of 7.2 times and 1.2 times in arabinofuranosidase and xylosidase activities, respectively. Reducing sugar yield and cellulose conversion of corn stover and corn fiber by RE-4-2-AraRA731V were further increased.
Two newly duplicated copies of genomic DNA are held together by the ring-shaped cohesin complex to ensure faithful inheritance of the genome during cell division1–3. Cohesin mediates sister chromatid cohesion by topologically entrapping two sister DNAs during DNA replication4,5, but how cohesion is established at the replication fork is poorly understood. Here, we studied the interplay between cohesin and replication by reconstituting a functional replisome using purified proteins. Once DNA is encircled before replication, the cohesin ring accommodates replication in its entirety, from initiation to termination, leading to topological capture of newly synthesized DNA. This suggests that topological cohesin loading is a critical molecular prerequisite to cope with replication. Paradoxically, topological loading per se is highly rate limiting and hardly occurs under the replication-competent physiological salt concentration. This inconsistency is resolved by the replisome-associate
The assembly and specification of synapses in the brain is incompletely understood1–3. Latrophilin-3 (encoded by Adgrl3, also known as Lphn3)—a postsynaptic adhesion G-protein-coupled receptor—mediates synapse formation in the hippocampus4 but the mechanisms involved remain unclear. Here we show in mice that LPHN3 organizes synapses through a convergent dual-pathway mechanism: activation of Gαs signalling and recruitment of phase-separated postsynaptic protein scaffolds. We found that cell-type-specific alternative splicing of Lphn3 controls the LPHN3 G-protein-coupling mode, resulting in LPHN3 variants that predominantly signal through Gαs or Gα12/13. CRISPR-mediated manipulation of Lphn3 alternative splicing that shifts LPHN3 from a Gαs- to a Gα12/13-coupled mode impaired synaptic connectivity as severely as the overall deletion of Lphn3, suggesting that Gαs signalling by LPHN3 splice variants mediates synapse formation. Notably, Gα