Diverse mechanisms of DDX3Y suppression by DDX3X DOI Creative Commons

Xiaolu Xu,

Shuo Wei

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

Abstract The DEAD-box RNA helicase DDX3X has important roles in development and disease. Loss of during developmental pathological processes such as tumorigenesis can lead to compensatory upregulation the close paralog DDX3Y males, which may underlie sexual dimorphism displayed by some DDX3X-associated diseases. However, how cross-regulates remains largely unknown. Here, we investigated regulation two male-derived human cancer cell lines, HCT116 U87MG. Depletion cells results moderately increased mRNA protein, part due stabilization transcripts. Conversely, reduction U87MG markedly upregulates protein without affecting its mRNA, mainly enhancing stability. We further show that physically interacts with DDX3Y. is much less stable than cells, substitution lysine residues corresponding arginine stabilizes Thus, following loss occur at either transcript or level, suggesting complex type-specific cross-regulation between these X- Y-linked paralogs keep total DDX3 dosage check.

Language: Английский

A subpopulation of cortical neurons altered by mutations in the autism risk gene DDX3X DOI Creative Commons
Michael Flores, Marta García-Forn,

Alexa von Mueffling

et al.

Biology Open, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 15, 2025

ABSTRACT Cell fate decisions during cortical development sculpt the identity of long-range connections that subserve complex behaviors. These are largely dictated by mutually exclusive transcription factors, including CTIP2/Bcl11b for subcerebral projection neurons and BRN1/Pou3f3 intra-telencephalic neurons. We have recently reported balance CTIP2-expressing is altered in a mouse model DDX3X syndrome, female-biased neurodevelopmental disorder associated with intellectual disability, autism spectrum disorder, significant motor challenges. Here, we studied developmental dynamics subpopulation co-expressing CTIP2 BRN1. found CTIP2+BRN1+ born early phases neurogenesis like other CTIP2+ neurons, peak expression perinatal life, persist adult brains. also excessive number prenatal mature areas Ddx3x mutant mice, translating into laminar distribution extending axons to brainstem. findings underscore critical role molecular specification health disease.

Language: Английский

Citations

2
Diverse mechanisms of DDX3Y suppression by DDX3X DOI Creative Commons

Xiaolu Xu,

Shuo Wei

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 9, 2025

Abstract The DEAD-box RNA helicase DDX3X has important roles in development and disease. Loss of during developmental pathological processes such as tumorigenesis can lead to compensatory upregulation the close paralog DDX3Y males, which may underlie sexual dimorphism displayed by some DDX3X-associated diseases. However, how cross-regulates remains largely unknown. Here, we investigated regulation two male-derived human cancer cell lines, HCT116 U87MG. Depletion cells results moderately increased mRNA protein, part due stabilization transcripts. Conversely, reduction U87MG markedly upregulates protein without affecting its mRNA, mainly enhancing stability. We further show that physically interacts with DDX3Y. is much less stable than cells, substitution lysine residues corresponding arginine stabilizes Thus, following loss occur at either transcript or level, suggesting complex type-specific cross-regulation between these X- Y-linked paralogs keep total DDX3 dosage check.

Language: Английский

Citations

0