Psychiatry related information on Tsn

• Here, we report that translin knock-out mice also exhibit sex-specific differences in tests of learning and memory, locomotor activity, anxiety-related behavior, and sensorimotor gating, as well as handling-induced seizures and alterations in monoamine neurotransmitter levels in several forebrain regions [1].
• Our results in mice indicate that mutations in translin may contribute to fragile X-like syndromes, mental retardation, attention deficit hyperactivity disorder, epilepsy, and autism spectrum disorders in humans [1].

High impact information on Tsn

• The kinesin KIF17b and RNA-binding protein TB-RBP transport specific cAMP-responsive element modulator-regulated mRNAs in male germ cells [2].
• We conclude that KIF17b serves as a molecular motor component of a TB-RBP-mouse ribonucleoprotein complex transporting a group of specific CREM-regulated mRNAs in mammalian male postmeiotic germ cells [2].
• Testis brain RNA-binding protein (TB-RBP), the mouse orthologue of the human protein Translin, is a widely expressed and highly conserved protein with proposed functions in chromosomal translocations, mitotic cell division, and mRNA transport, stabilization, and storage [2].
• Combining in situ hybridization and immunohistochemistry at the electron microscope level, a temporally sequential dissociation of KIF17b and TB-RBP from specific mRNAs is detected with TB-RBP release coincident with the time of mRNA translation, indicating a separation of the processes of transport and translation [2].
• The mouse RNA-binding protein, TB-RBP, suppresses translation in vitro and attaches mRNAs to microtubules by binding to conserved elements in the 3' untranslated regions of specific mRNAs [3].

Biological context of Tsn

• In contrast, TB-RBP is present in both the nuclei and cytoplasm of transfected cells and uses a highly conserved nuclear export signal to exit nuclei [4].
• As an RNA-binding protein, TB-RBP binds to conserved sequence elements often present in the 3' untranslated regions (UTRs) of specific mRNAs modulating their translation and transport [5].
• Moreover, the Gapds mRNA is the first mRNA shown to have a functional TB-RBP binding site in its 5' UTR [5].
• These data suggest that TB-RBP is involved in the posttranscriptional regulation of Gapds gene expression during spermiogenesis [5].
• When the putative GTP binding site of TB-RBP, amino acid sequence VTAGD, is altered to VTNSD by site directed mutagenesis, GTP will no longer bind to TB-RBP(GTP) and TB-RBP(GTP) no longer binds to RNA, although DNA binding is not affected [6].

Anatomical context of Tsn

• Western blot analysis of germ cell protein extracts reveals an increased ratio of TRAX to TB-RBP in meiotic pachytene spermatocytes compared with the post-meiotic round and elongated spermatids [7].
• Here we show that TB-RBP binds specific mRNAs to microtubules (MTs) in vitro [8].
• TB-RBP-null male mice were fertile and sired offspring but had abnormal seminiferous tubules and reduced sperm counts [9].
• To determine the functions of the DNA/RNA-binding protein TB-RBP in somatic cells, we examined cultured primary mouse embryonic fibroblasts (MEFs) derived from TB-RBP-deficient mice [10].
• It is also possible that BC1 RNP or Translin itself may play a regulatory role(s) in the translation of mRNAs within dendrites [11].

Associations of Tsn with chemical compounds

• Mouse testis brain RNA-binding protein/translin selectively binds to the messenger RNA of the fibrous sheath protein glyceraldehyde 3-phosphate dehydrogenase-S and suppresses its translation in vitro [5].
• We find that the mouse TB-RBP cDNAs contain an open reading frame of 228 amino acids with a leucine zipper domain within its C terminus, a transmembrane helix, and a group of putative phosphorylation sites [3].
• Serum Tsn-alpha 1 and corticosterone levels were determined by radioimmunoassay [12].
• Although GADD34 expression was significantly elevated with methyl methanesulfonate treatment, we could not detect the induction of Translin mRNA [13].

Physical interactions of Tsn

• Translin associated factor X (TRAX) is a binding partner of TB-RBP/Translin [14].
• The single copy mouse Testis Brain RNA-Binding Protein (TB-RBP) gene encodes three mRNAs of 3.0, 1.7, and 1.0 kb which only differ in their 3' UTRs [15].

Co-localisations of Tsn

• Mouse testis brain ribonucleic acid-binding protein/translin colocalizes with microtubules and is immunoprecipitated with messenger ribonucleic acids encoding myelin basic protein, alpha calmodulin kinase II, and protamines 1 and 2 [16].

Regulatory relationships of Tsn

• In vitro translation assays revealed that Gapds mRNA translation was inhibited by recombinant TB-RBP or by a TB-RBP mutant protein, Nb, capable of binding RNA [5].

Other interactions of Tsn

• In addition to a leucine zipper, two basic domains in TB-RBP are essential for RNA binding, but only one of these domains is needed for DNA binding [4].
• No translational inhibition by recombinant TB-RBP was seen with Gapds mRNA lacking the H element [5].
• The testis brain RNA-binding protein (TB-RBP) functions as an RNA-binding protein in brain and testis, binding to conserved sequence elements present in specific mRNAs, such as protamine 1 and 2 [17].
• AKAP4 mRNA forms a complex with TB-RBP and the Ter ATPase in nuclei and remains associated with these proteins as it exits nuclei into the cytoplasm and as it passes through intercellular bridges between spermatids [17].

Analytical, diagnostic and therapeutic context of Tsn

• To identify additional mRNA targets of TB-RBP, immunoprecipitation and reverse transcription-polymerase chain reaction (RT-PCR) assays were carried out using an affinity-purified antibody to TB-RBP with testicular extracts [5].
• Tsn-null males show a reduced sperm count and high levels of apoptosis in meiotic cells, suggesting a critical function for TSN during meiosis [18].
• Gel shift analysis of double- and single-stranded DNA showed that translin binds to single-stranded DNA, but its transcriptional activation is independent of DNA binding [19].
• Confocal microscopy confirmed colocalization of TB-RBP and tubulin in the cytoplasm of male germ cells [16].
• Using a cDNA encoding TB-RBP, the gene copy number and the developmental expression of TB-RBP have been analyzed by Southern blotting, Northern blotting, and in situ hybridization [20].

References