The mRNA Encoding τCstF‐64 Is Expressed Ubiquitously in Mouse Tissues

Huber, Zane; Monarez, Roberto R.; Dass, Brinda; MacDonald, Clinton C.

doi:10.1196/annals.1336.017

Cited by 10 publications

(15 citation statements)

References 45 publications

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“…τCstF-64 was detected in extracts from wild type mouse testis and brain (lanes 1 and 3), but not in liver (lane 5), consistent with earlier reports using the 6A9 antibody [40–42]. τCstF-64 was detected at similar levels in both neurons isolated from wild type juvenile rats (lane 7) and in C6 rat glial cells [50], suggesting that τCstF-64 is distributed equally between neurons and glia in rodent brain.…”

Section: Resultssupporting

confidence: 91%

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The Cstf2t Polyadenylation Gene Plays a Sex-Specific Role in Learning Behaviors in Mice

et al. 2016

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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.

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Section: Resultssupporting

confidence: 91%

“…Similarly, CstF-64 was expressed in isolated wild type rat neuronal and glial cells (lanes 7, 8). This confirmed expression of both CstF-64 and τCstF-64 in testis and brain [40–42]. The apparent slower migration of CstF-64 in the samples from liver (lanes 5, 6) has been observed previously [36, 40, 41, 45].…”

Section: Resultssupporting

confidence: 85%

The Cstf2t Polyadenylation Gene Plays a Sex-Specific Role in Learning Behaviors in Mice

et al. 2016

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“…These results suggest that our CstF64τ antibody is highly specific, and our Western analyses demonstrate that CstF64τ, similar to CstF64, is widely expressed. This is consistent with previous reports that CstF64τ mRNAs are detected ubiquitously in mouse tissues (Huber et al 2005). However, given that the CstF64:CstF64τ ratio and the total levels of these CstF64 and CstF64τ in mRNA 3 ′ processing www.rnajournal.org 1787 two proteins are highly variable in different tissues (Fig.…”

Section: Discussionsupporting

confidence: 81%

“…However, the functions of CstF64τ in mRNA 3 ′ processing and APA regulation and its functional relationship with CstF64 are still poorly characterized. For examples, it has been shown that CstF64τ mRNAs are detected ubiquitously in mouse tissues, and it is unclear how testis-specific expression of CstF64τ proteins is achieved (Huber et al 2005). In addition, we and others have shown recently that CstF64 depletion in human cells has relatively little effect on the global APA profile (Martin et al 2012;Yao et al 2012), but codepletion of both CstF64 and CstF64τ leads to greater APA changes.…”

Section: Mrnamentioning

confidence: 99%

Overlapping and distinct functions of CstF64 and CstF64τ in mammalian mRNA 3′ processing

Yao

Choi

Weng

et al. 2013

RNA

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mRNA 3′ processing is dynamically regulated spatially and temporally. However, the underlying mechanisms remain poorly understood. CstF64τ is a paralog of the general mRNA 3 ′ processing factor, CstF64, and has been implicated in mediating testis-specific mRNA alternative polyadenylation (APA). However, the functions of CstF64τ in mRNA 3 ′ processing have not been systematically investigated. We carried out a comprehensive characterization of CstF64τ and compared its properties to those of CstF64. In contrast to previous reports, we found that both CstF64 and CstF64τ are widely expressed in mammalian tissues, and their protein levels display tissue-specific variations. We further demonstrated that CstF64 and CstF64τ have highly similar RNA-binding specificities both in vitro and in vivo. CstF64 and CstF64τ modulate one another's expression and play overlapping as well as distinct roles in regulating global APA profiles. Interestingly, protein interactome analyses revealed key differences between CstF64 and CstF64τ, including their interactions with another mRNA 3 ′ processing factor, symplekin. Together, our study of CstF64 and CstF64τ revealed both functional overlap and specificity of these two important mRNA 3 ′ processing factors and provided new insights into the regulatory mechanisms of mRNA 3 ′ processing.

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“…Although its mRNA is present in most tissues (Huber, Monarez, Dass, & MacDonald, 2005), in mouse the protein is found almost exclusively in testis (Wallace et al, 1999). The τCstf-64 protein has a partially repetitive Gly/Gln-rich insertion of 30 amino acids in between the second and third CstF-64 phosphorylation sites described above, between Gly517 and Ser518.…”

Section: Cleavage Stimulationmentioning

confidence: 99%

Finishing touches: Post-translational modification of protein factors involved in mammalian pre-mRNA 3′ end formation

Ryan

Bauer

2008

The International Journal of Biochemistry & Cell Biology

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In eukaryotes, a pre-messenger RNA (pre-mRNA) must undergo several processing reactions before it is exported to the cytoplasm for translation. One of these reactions, endonucleolytic 3′ cleavage at the polyadenylation site, prepares the pre-mRNA for addition of the poly(A) tail and defines the 3′ untranslated region (UTR), which typically contains important gene expression regulatory sequences. While the protein factors responsible for the endonucleolytic cleavage have been largely identified, the means by which their action is limited to the 3′ end of the transcription unit and coordinated with other co-transcriptional events remains unclear. In this review, we summarize and review recent findings revealing that the mammalian 3′ cleavage factors undergo extensive post-translational modification. These modifications include: arginine methylation, lysine sumoylation, lysine acetylation, and the phosphorylation of serine, threonine and tyrosine residues. Every cleavage factor, though not every subunit, is affected. Human Fip1 and the 59 kD subunit of Cleavage Factor I emerge as the most frequently modified core cleavage factor subunits. We outline and compare the various proteomic methods that have uncovered these modifications, and review emerging hypotheses concerning their function. The roles of these covalent but reversible modifications in other systems suggest that 3′ end formation in mammals relies upon post-translational modification for proper function and regulation.

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The mRNA Encoding τCstF‐64 Is Expressed Ubiquitously in Mouse Tissues

Cited by 10 publications

References 45 publications

The Cstf2t Polyadenylation Gene Plays a Sex-Specific Role in Learning Behaviors in Mice

The Cstf2t Polyadenylation Gene Plays a Sex-Specific Role in Learning Behaviors in Mice

Overlapping and distinct functions of CstF64 and CstF64τ in mammalian mRNA 3′ processing

Finishing touches: Post-translational modification of protein factors involved in mammalian pre-mRNA 3′ end formation

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