Genetic loss of importin α4 causes abnormal sperm morphology and impacts on male fertility in mouse

2020 ◽  
Vol 34 (12) ◽  
pp. 16224-16242
Author(s):  
Yoichi Miyamoto ◽  
Mitsuho Sasaki ◽  
Haruhiko Miyata ◽  
Yoko Monobe ◽  
Masahiro Nagai ◽  
...  
2019 ◽  
Author(s):  
Jordan P. Lewandowski ◽  
Gabrijela Dumbović ◽  
Audrey R. Watson ◽  
Taeyoung Hwang ◽  
Emily Jacobs-Palmer ◽  
...  

ABSTRACTBackgroundSeveral long noncoding RNAs (lncRNAs) have been shown to function as central components of molecular machines that play fundamental roles in biology. While the number of annotated lncRNAs in mammalian genomes has greatly expanded, their functions remain largely uncharacterized. This is compounded by the fact that identifying lncRNA loci that have robust and reproducible phenotypes when mutated has been a challenge.ResultsWe previously generated a cohort of 20 lncRNA loci knockout mice. Here, we extend our initial study and provide a more detailed analysis of the highly conserved lncRNA locus, Taurine Upregulated Gene 1 (Tug1). We report that Tug1 knockout male mice are sterile with complete penetrance due to a low sperm count and abnormal sperm morphology. Having identified a lncRNA loci with a robust phenotype, we wanted to determine which, if any, potential elements contained in the Tug1 genomic region (DNA, RNA, protein, or the act of transcription) have activity. Using engineered mouse models and cell-based assays, we provide evidence that the Tug1 locus harbors three distinct regulatory activities – two noncoding and one coding: (i) a cis DNA repressor that regulates many neighboring genes, (ii) a lncRNA that can regulate genes by a trans-based function, and finally (iii) Tug1 encodes an evolutionary conserved peptide that when overexpressed impacts mitochondrial membrane potential.ConclusionsOur results reveal an essential role for the Tug1 locus in male fertility and uncover three distinct regulatory activities in the Tug1 locus, thus highlighting the complexity present at lncRNA loci.


1992 ◽  
Vol 28 (1) ◽  
pp. 39-41 ◽  
Author(s):  
J. H. Check ◽  
A. Bollendorf ◽  
M. Press ◽  
T. Blue

2019 ◽  
Vol 112 (4) ◽  
pp. e61-e66 ◽  
Author(s):  
Thinus F. Kruger ◽  
Anibal A. Acosta ◽  
Kathryn F. Simmons ◽  
R. James Swanson ◽  
James F. Matta ◽  
...  

2008 ◽  
Vol 29 (5) ◽  
pp. 540-548 ◽  
Author(s):  
C. Gazquez ◽  
J. Oriola ◽  
S. de Mateo ◽  
J. M. Vidal-Taboada ◽  
J. L. Ballesca ◽  
...  

2013 ◽  
Vol 189 (4S) ◽  
Author(s):  
James Hotaling ◽  
Gulum Kosova ◽  
Samuel Ohlander ◽  
Craig Niederberger ◽  
Gail S. Prins ◽  
...  

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