Anti-QKI monoclonal antibody Made to order

The quaking (qkI) gone produces three major alternatively spliced variants (qkI-5,-6,-7) that encode for proteins that share the RNA binding, KH domain. Previous studies utilizing the qk(k2) allele, which contains an N-ethyl-N-nitrosourea (ENU)-induced point mutation in the KH domain, demonstrate that this functional region of qkI is required for embryonic vascular development. In the current studies we demonstrate that qk(I-1)/qk(I-1) mutants, which lack the QKI-5 splice variant, also died at midgestation due to vascular remodeling defects. In addition, although all three QKI isoforms were expressed in the visceral endoderm of wildtype yolk sacs, qkI-6 and qkI-7 transcript and protein expression were suppressed in qk(k2)/qk(k2) and qk(I-1)/qk(I-1) mutant yolk sacs, suggesting that the KH-domain of QKI-5 was required for qk1-6 and qkI-7 expression. Further studies revealed that the cellular role of qkI is to regulate visceral endoderm function, including the local synthesis of retinoic acid (RA) and the subsequent control of endothelial cell proliferation, matrix production, and visceral endoderm survival. Although these defects were rescued by exogenous RA, visceral endoderm function or vascular remodeling were not restored. Thus, we conclude that qkI regulates visceral endoderm function, which is critical for vascular remodeling.

Schizophrenia (SZ) is a complex disease characterized by impaired neuronal functioning. Although defective alternative splicing has been linked to SZ, the molecular mechanisms responsible are unknown. Additionally, there is limited understanding of the early transcriptomic responses to neuronal activation. Here, we profile these transcriptomic responses and show that long non-coding RNAs (IncRNAs) are dynamically regulated by neuronal activation, including acute downregulation of the IncRNA Gomafu, previously implicated in brain and retinal development. Moreover, we demonstrate that Gomafu binds directly to the splicing factors QKI and SRSF1 (serine/arginine-rich splicing factor 1) and dysregulation of Gomafu leads to alternative splicing patterns that resemble those observed in SZ for the archetypal SZ-associated genes DISC1 and ERBB4. Finally, we show that Gomafu is downregulated in post-mortem cortical gray matter from the superior temporal gyrus in SZ. These results functionally link activity-regulated lncRNAs and alternative splicing in neuronal function and suggest that their dysregulation may contribute to neurological disorders.