High levels of the cold shock protein Y-box-binding protein-1, YB-1, are tightly correlated with increased cell proliferation and progression. However, the precise mechanism by which YB-1 regulates proliferation is unknown. Here, we found that YB-1 depletion in several cancer cell lines and in immortalized fibroblasts resulted in cytokinesis failure and consequent multinucleation. Rescue experiments indicated that YB-1 was required for completion of cytokinesis. Using confocal imaging we found that YB-1 was essential for orchestrating the spatio-temporal distribution of the microtubules, β-actin and the chromosome passenger complex (CPC) to define the cleavage plane. We show that phosphorylation at six serine residues was essential for cytokinesis, of which novel sites were identified using mass spectrometry. Using atomistic modelling we show how phosphorylation at multiple sites alters YB-1 conformation, allowing it to interact with protein partners. Our results establish phosphorylated YB-1 as a critical regulator of cytokinesis, defining precisely how YB-1 regulates cell division.

Background PTRHD1 was proposed as a disease‐causing gene of intellectual disability, spasticity, and parkinsonism. Objectives To characterize the clinical phenotype and the molecular cause of intellectual disability in four affected individuals of a consanguineous family. Methods Clinical evaluation, whole‐exome sequencing, Sanger sequencing, reverse transcription polymerase chain reaction (PCR), real‐time PCR, immunoblot, and isoelectric focusing. Results A homozygous 28‐nucleotide frameshift deletion introducing a premature stop codon in the PTRHD1 exon 1 was identified in the four affected members. We further confirmed the apparent transcript escape of the nonsense‐mediated messenger RNA (mRNA) decay pathway. Real‐time PCR showed that mRNA expression of the mutant PTRHD1 is higher compared to the wild‐type. Western blotting and isoelectric focusing identified a truncated, but stable mutant PTRHD1 protein expressed in the patient's primary cells. Conclusions We provide further evidence that PTRHD1 mutations are associated with autosomal‐recessive childhood‐onset intellectual disability associated with spasticity and parkinsonism.

Next-generation sequencing, such as whole-exome sequencing (WES), is increasingly used in the study of Mendelian disorders, yet many are reported as “negative.” Inappropriate variant annotation and filtering steps are reasons for missing the molecular diagnosis. Noncoding variants, including splicing mutations, are examples of variants that can be overlooked. Herein, we report a family of four affected newborns, and all presented with severe congenital microcephaly. Initial research WES analysis identified a damaging homozygous variant in NME1 gene as a possible cause of primary microcephaly phenotype in these patients. However, reanalysis of the exome data uncovered a biallelic splice site variant in asparagine synthetase gene which seems to be the possible cause of the phenotype in these patients. This study highlights the importance of revisiting the exome data and the issue of “negative” exome and the afterward approaches to identify and prove new candidate genes.