The Cstf2t Polyadenylation Gene Plays a Sex-Specific Role in Learning Behaviors in Mice.
Polyadenylation is an essential mechanism for the processing of mRNA 3' ends. CstF-64 (the 64,000 Mr subunit of the cleavage stimulation factor; gene symbol Cstf2) is an RNA-binding protein that regulates mRNA polyadenylation site usage. We discovered a paralogous form of CstF-64 called τCstF-64 (Cstf2t). The Cstf2t gene is conserved in all eutherian mammals including mice and humans, but the τCstF-64 protein is expressed only in a subset of mammalian tissues, mostly testis and brain. Male mice that lack Cstf2t (Cstf2t-/- mice) experience disruption of spermatogenesis and are infertile, although female fertility is unaffected. However, a role for τCstF-64 in the brain has not yet been determined. Given the importance of RNA polyadenylation and splicing in neuronal gene expression, we chose to test the hypothesis that τCstF-64 is important for brain function. Male and female 185-day old wild type and Cstf2t-/- mice were examined for motor function, general activity, learning, and memory using rotarod, open field activity, 8-arm radial arm maze, and Morris water maze tasks. Male wild type and Cstf2t-/- mice did not show differences in learning and memory. However, female Cstf2t-/- mice showed significantly better retention of learned maze tasks than did female wild type mice. These results suggest that τCstf-64 is important in memory function in female mice. Interestingly, male Cstf2t-/- mice displayed less thigmotactic behavior than did wild type mice, suggesting that Cstf2t may play a role in anxiety in males. Taken together, our studies highlight the importance of mRNA processing in cognition and behavior as well as their established functions in reproduction.
Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
Jaryse C
JC
Harris
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
Joseph M
JM
Martinez
Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
Petar N
PN
Grozdanov
Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
Susan E
SE
Bergeson
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, Rhode Island, United States of America.
Paula
P
Grammas
Department of Cell Biology & Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas, United States of America.
Clinton C
http://orcid.org/0000-0003-3209-1982
CC
MacDonald
D000818:Animals; D001007:Anxiety / Q000235:genetics / Q000503:physiopathology; D001921:Brain / Q000166:cytology / Q000502:physiology; D039241:Cleavage Stimulation Factor / Q000172:deficiency / Q000235:genetics*; D003463:Cues; D005260:Female; D007858:Learning; D008124:Locomotion; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D026723:Polyadenylation; D012333:RNA, Messenger / Q000235:genetics; D012727:Sex Characteristics; D014796:Visual Perception
D039241:Cleavage Stimulation Factor; C492658:Cstf2t protein, mouse; D012333:RNA, Messenger