Testis-Brain RNA-Binding Protein, a Testicular Translational Regulatory RNA-Binding Protein, is Present in the Brain and Binds to the 3′ Untranslated Regions of Transported Brain mRNAs1

Han, Jian; Gu, Wei; Hecht, Norman B.

doi:10.1095/biolreprod53.3.707

Cited by 80 publications

(84 citation statements)

References 37 publications

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“…Like FMRP, translin shows highest expression in the testis and brain (Han et al, 1995b;Hergersberg et al, 1995;Gu et al, 1998;Finkenstadt et al, 2001). In the testis, translin binds translationally repressed mRNAs containing cis-acting motifs termed Y and H elements and accompanies these transcripts along intercellular bridges between spermatids (Morales et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Behavioral and Neurochemical Alterations in Mice Lacking the RNA-Binding Protein Translin

Stein¹,

Bergman²,

Fang³

et al. 2006

J. Neurosci.

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Synapse-specific local protein synthesis is thought to be important for neurodevelopment and plasticity and involves neuronal RNAbinding proteins that regulate the transport and translation of dendritically localized transcripts. The best characterized of these RNAbinding proteins is the fragile X mental retardation protein (FMRP). Mutations affecting the expression or function of FMRP cause fragile X syndrome in humans, and targeted deletion of the gene encoding FMRP results in developmental and behavioral alterations in mice. Translin is an RNA-binding protein that regulates mRNA transport and translation in mouse male germ cells and is proposed to play a similar role in neurons. Like FMRP, translin is present in neuronal dendrites, binds dendritically localized RNA, and associates with microtubules and motor proteins. We reported previously the production of viable homozygous translin knock-out mice, which demonstrate altered expression of multiple mRNA transcripts in the brain and mild motor impairments. 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. Similar behavioral and neurochemical alterations have been observed in mice lacking FMRP, suggesting that both proteins may act within the same neuronal systems and signaling pathways. 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.

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Section: Introductionmentioning

confidence: 99%

Behavioral and Neurochemical Alterations in Mice Lacking the RNA-Binding Protein Translin

Stein¹,

Bergman²,

Fang³

et al. 2006

J. Neurosci.

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“…Accordingly, it is thought to play a role in the subcellular transport and/or translational control of its target RNAs in these tissues (Han et al 1995a;Kobayashi et al 1998;Morales et al 1998;Muramatsu et al 1998;Wu and Hecht 2000;Yang et al 2003). Unlike Translin, Trax does not bind nucleic acids directly, but might be part of the RNA-or DNA-binding complex, thereby modulating the nucleic-acid-binding affinity of Translin (Chennathukuzhi et al 2001;Finkenstadt et al 2002;Gupta et al 2005).…”

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confidence: 99%

Functional Characterization of Drosophila Translin and Trax

Claußen¹,

Koch²,

Jin³

et al. 2006

Genetics

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The vertebrate RNA and ssDNA-binding protein Translin has been suggested to function in a variety of cellular processes, including DNA damage response, RNA transport, and translational control. The Translin-associated factor X (Trax) interacts with Translin, and Trax protein stability depends on the presence of Translin. To determine the function of the Drosophila Translin and Trax, we generated a translin null mutant and isolated a trax nonsense mutation. translin and trax single and double mutants are viable, fertile, and phenotypically normal. Meiotic recombination rates and chromosome segregation are also not affected in translin and trax mutants. In addition, we found no evidence for an increased sensitivity for DNA double-strand damage in embryos and developing larvae. Together with the lack of evidence for their involvement in DNA double-strand break checkpoints, this argues against a critical role for Translin and Trax in sensing or repairing such DNA damage. However, Drosophila translin is essential for stabilizing the Translin interaction partner Trax, a function that is surprisingly conserved throughout evolution. Conversely, trax is not essential for Translin stability as trax mutants exhibit normal levels of Translin protein.

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“…Translin/TB-RBP is expressed in many organisms, including fission yeasts, plants, frogs, insects, and mammals. In mammalian tissues, it is ubiquitously expressed, with especially high levels in the brain and testis (18,31,32). Translin is a 228-amino-acid protein encoded by a single-copy gene on human chromosome 2 (3).…”

mentioning

confidence: 99%

Mice Deficient for Testis-Brain RNA-Binding Protein Exhibit a Coordinate Loss of TRAX, Reduced Fertility, Altered Gene Expression in the Brain, and Behavioral Changes

Chennathukuzhi

Stein

Abel

et al. 2003

Molecular and Cellular Biology

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106

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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 and storage. To better define the biological roles of TB-RBP, we generated mice lacking TB-RBP. Matings between heterozygotes gave rise to viable, apparently normal homozygous mutant mice at a normal Mendelian ratio. The TB-RBP-related and -interacting protein Translin-associated factor X was reduced to 50% normal levels in heterozygotes and was absent in TB-RBP-null animals. The null mice were 10 to 30% smaller than their wild-type or heterozygote littermates at birth and remained so to about 6 to 9 months of age, showed normal B-and T-cell development, and accumulated visceral fat. TB-RBP-null male mice were fertile and sired offspring but had abnormal seminiferous tubules and reduced sperm counts. Null female mice were subfertile and had reduced litter sizes. Microarray analysis of total brain RNA from null and wild-type mice revealed an altered gene expression profile with the up-regulation of 14 genes and the down-regulation of 217 genes out of 12,473 probe sets. Numerous neurotransmitter receptors and ion channels, including ␥-aminobutyric acid A receptor ␣1 and glutamate receptor ␣3, were strongly down-regulated. Behavioral abnormalities were also seen. Compared to littermates, the TB-RBP-null mice appeared docile and exhibited reduced Rota-Rod performance.The mouse nucleic acid-binding protein testis-brain RNAbinding protein (TB-RBP) is the orthologue of the human protein Translin (5, 6, 26). The official nomenclature for the mouse TB-RBP gene is Tsn. Translin/TB-RBP is expressed in many organisms, including fission yeasts, plants, frogs, insects, and mammals. In mammalian tissues, it is ubiquitously expressed, with especially high levels in the brain and testis (18,31,32). Translin is a 228-amino-acid protein encoded by a single-copy gene on human chromosome 2 (3). TB-RBP, encoded by a single-copy gene on mouse chromosome 1, differs from the human protein in three amino acids (3,55,56). Translin has been implicated in DNA rearrangements through binding to single-stranded DNA sequences found at the breakpoint junctions of chromosomal translocations in lymphoid malignancies and solid tumors (26). Electron microscopic and analytical ultracentrifugation studies have revealed multimeric ring structures of Translin which have been proposed to recognize staggered breaks occurring at recombination hot spots in the genome (26,35,45,52). Similar multimeric ring structures are seen when TB-RBP is crystallized (44). Recently, Translin was shown to accelerate cell proliferation when overexpressed in cultured HEK cells (22).In addition to its proposed roles in DNA recombination and cell proliferation, TB-RBP functions in mRNA transport and/or stabilization and in translational regulation (40,41). In the brain and testis, TB-RBP serves as a linker protein binding specific mRNAs t...

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Testis-Brain RNA-Binding Protein, a Testicular Translational Regulatory RNA-Binding Protein, is Present in the Brain and Binds to the 3′ Untranslated Regions of Transported Brain mRNAs1

Cited by 80 publications

References 37 publications

Behavioral and Neurochemical Alterations in Mice Lacking the RNA-Binding Protein Translin

Behavioral and Neurochemical Alterations in Mice Lacking the RNA-Binding Protein Translin

Functional Characterization of Drosophila Translin and Trax

Mice Deficient for Testis-Brain RNA-Binding Protein Exhibit a Coordinate Loss of TRAX, Reduced Fertility, Altered Gene Expression in the Brain, and Behavioral Changes

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