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Most pseudogenes are generated when an RNA transcript is reverse-transcribed and integrated into the genome at a new location. Pseudogenes are often considered as an imperfect and silent copy of a functional gene because of the accumulation of numerous mutations in their sequence. Here we report the presence of Pfh8-ps , a Phf8 retrotransposed pseudogene in the mouse genome, which has no disruptions in its coding sequence. We show that this pseudogene is mainly transcribed in testis and can produce a PHF8-PS protein in vivo. As the PHF8-PS protein has a well-conserved JmjC domain, we characterized its enzymatic activity and show that PHF8-PS does not have the intrinsic capability to demethylate H3K9me2 in vitro compared to the parental PHF8 protein. Surprisingly, PHF8-PS does not localize in the nucleus like PHF8, but rather is mostly located at the cytoplasm. Finally, our proteomic analysis of PHF8-PS-associated proteins revealed that PHF8-PS interacts not only with mitochondrial proteins, but also with prefoldin subunits (PFDN proteins) that deliver unfolded proteins to the cytosolic chaperonin complex implicated in the folding of cytosolic proteins. Together, our findings highlighted PHF8-PS as a new pseudogene-derived protein with distinct molecular functions from PHF8.

The pluripotency and differentiation states of embryonic stem cells (ESCs) are regulated by a set of core transcription factors, primarily Sox2, Oct4, and Nanog. Although their transcriptional regulation has been studied extensively, the contribution of posttranslational modifications in Sox2, Oct4, and Nanog are poorly understood. Here, using a CRISPR-Cas9 knockout library screen in murine ESCs, we identify the E3 ubiquitin ligase Stub1 as a negative regulator of pluripotency. Manipulation of Stub1 expression in murine ESCs shows that ectopic Stub1 expression significantly reduces the protein half-life of Sox2, Oct4, and Nanog. Mechanistic investigations reveal Stub1 catalyzes the polyubiquitination and 26S proteasomal degradation of Sox2 and Nanog through K48-linked ubiquitin chains and Oct4 via K63 linkage. Stub1 deficiency positively enhances somatic cell reprogramming and delays differentiation, whereas its enforced expression triggers ESC differentiation. The discovery of Stub1 as an integral pluripotency regulator strengthens our understanding of ESC regulation beyond conventional transcriptional control mechanisms., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Congenital cataract is the cloudiness of the eye's natural lens and is a primary cause of congenital vision loss. It accounts for almost 10% of childhood vision loss worldwide., Methods: A four generation Chinese family having seven affected individuals was recruited for the current study. Exome sequencing was performed to identify the genetic cause of congenital cataract., Results: Analysis of data identified a novel frameshift mutation, c.608delC (p.A203fs), in the PITX3 gene. This mutation was only observed in the affected individuals while the unaffected members of the family as well as 100 ethnically matched normal controls did not contain this deletion., Conclusion: These findings suggest that p.A203fs is the cause of cataracts in the recruited family. This information would be further helpful in the genetic diagnosis of cataract and in the genetic counseling of similar patients., (© 2017 by the Association of Clinical Scientists, Inc.)

The TP53 gene product, p53, is a pleiotropic transcription factor induced by stress, which functions to promote cell cycle arrest, apoptosis and senescence. Genome-wide profiling has revealed an extensive system of long noncoding RNAs (lncRNAs) that is integral to the p53 signalling network. As a research tool, we implemented a public access database called TP53LNC-DB that annotates currently available information relating lncRNAs to p53 signalling in humans. [ABSTRACT FROM AUTHOR]