TY - JOUR
T1 - DDX3Y, a male-specific region of y chromosome gene, may modulate neuronal differentiation
AU - Vakilian, Haghighat
AU - Mirzaei, Mehdi
AU - Sharifi Tabar, Mehdi
AU - Pooyan, Paria
AU - Habibi Rezaee, Lida
AU - Parker, Lindsay
AU - Haynes, Paul A.
AU - Gourabi, Hamid
AU - Baharvand, Hossein
AU - Salekdeh, Ghasem Hosseini
PY - 2015/9/4
Y1 - 2015/9/4
N2 - Although it is apparent that chromosome complement mediates sexually dimorphic expression patterns of some proteins that lead to functional differences, there has been insufficient evidence following the manipulation of the male-specific region of the Y chromosome (MSY) gene expression during neural development. In this study, we profiled the expression of 23 MSY genes and 15 of their X-linked homologues during neural cell differentiation of NTERA-2 human embryonal carcinoma cell line (NT2) cells in three different developmental stages using qRT-PCR, Western blotting, and immunofluorescence. The expression level of 12 Y-linked genes significantly increased over neural differentiation, including RBMY1, EIF1AY, DDX3Y, HSFY1, BPY2, PCDH11Y, UTY, RPS4Y1, USP9Y, SRY, PRY, and ZFY. We showed that siRNA-mediated knockdown of DDX3Y, a DEAD box RNA helicase enzyme, in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after DDX3Y knockdown. Among 917 reproducibly identified proteins detected, 71 proteins were differentially expressed following DDX3Y siRNA treatment compared with mock treated cells. Functional grouping indicated that these proteins were involved in cell cycle, RNA splicing, and apoptosis, among other biological functions. Our results suggest that MSY genes may play an important role in neural differentiation and demonstrate that DDX3Y could play a multifunctional role in neural cell development, probably in a sexually dimorphic manner.
AB - Although it is apparent that chromosome complement mediates sexually dimorphic expression patterns of some proteins that lead to functional differences, there has been insufficient evidence following the manipulation of the male-specific region of the Y chromosome (MSY) gene expression during neural development. In this study, we profiled the expression of 23 MSY genes and 15 of their X-linked homologues during neural cell differentiation of NTERA-2 human embryonal carcinoma cell line (NT2) cells in three different developmental stages using qRT-PCR, Western blotting, and immunofluorescence. The expression level of 12 Y-linked genes significantly increased over neural differentiation, including RBMY1, EIF1AY, DDX3Y, HSFY1, BPY2, PCDH11Y, UTY, RPS4Y1, USP9Y, SRY, PRY, and ZFY. We showed that siRNA-mediated knockdown of DDX3Y, a DEAD box RNA helicase enzyme, in neural progenitor cells impaired cell cycle progression and increased apoptosis, consequently interrupting differentiation. Label-free quantitative shotgun proteomics based on a spectral counting approach was then used to characterize the proteomic profile of the cells after DDX3Y knockdown. Among 917 reproducibly identified proteins detected, 71 proteins were differentially expressed following DDX3Y siRNA treatment compared with mock treated cells. Functional grouping indicated that these proteins were involved in cell cycle, RNA splicing, and apoptosis, among other biological functions. Our results suggest that MSY genes may play an important role in neural differentiation and demonstrate that DDX3Y could play a multifunctional role in neural cell development, probably in a sexually dimorphic manner.
KW - Chromosome-Centric Human Proteome Project (C-HPP)
KW - Cell-Based Human Proteome Project
KW - Y-linked genes
KW - DDX3Y
KW - shotgun proteomics
KW - apoptosis
KW - cell cycle
KW - RNA metabolism
UR - http://www.scopus.com/inward/record.url?scp=84941078091&partnerID=8YFLogxK
U2 - 10.1021/acs.jproteome.5b00512
DO - 10.1021/acs.jproteome.5b00512
M3 - Article
C2 - 26144214
AN - SCOPUS:84941078091
SN - 1535-3893
VL - 14
SP - 3474
EP - 3483
JO - Journal of Proteome Research
JF - Journal of Proteome Research
IS - 9
ER -