Binding of a phosphoprotein to the 3' untranslated region of the mouse protamine 2 mRNA temporally represses its translation.

Kwon, Yunhee Kim; Hecht, Norman B.

doi:10.1128/mcb.13.10.6547

Cited by 151 publications

(114 citation statements)

References 60 publications

(65 reference statements)

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“…Synthesis of a translational activator, like a protein kinase or phosphatase that modifies the mRNP, is a possibility. The RNA-binding properties of TB-RBP appear to be coupled to its phosphorylation status 23,24 and are consistent with such a model. Of course, synthesis of a translational activator of the protamine mRNAs only tells us how activation of protamine translation is achieved.…”

Section: Activation Of Translationally Repressed Mrnassupporting

confidence: 61%

“…To elucidate the mechanisms of translational regulation it is important to identify all of the factors involved. Despite significant progress in identifying protamine RNA-binding proteins, none of the proteins thus far described, PRBP, 41 TB-RBP, 23,24 or the 48r50 kDa Y box proteins, 39 have been shown to mediate the translational repression of the protamine mRNAs in vivo. Certain properties of these proteins, for example, the sequence-specific binding properties of the 48r50-kDa Y box proteins and TB-RBP, the ability of the binding site for the 48r50-kDa proteins to repress translation in vivo and the presence of the PRBP-binding site in a region of the Prm-1 3Ј UTR shown to be sufficient for translational repression in transgenic mice, are desirable for putative translational repressors.…”

Section: Perspectivesmentioning

confidence: 99%

“…The Y and H elements of Prm-2 have been shown to mediate translational repression of a reporter mRNA in a rabbit reticulocyte lysate supplemented with a testis extract enriched for the binding factor, suggesting that the site is capable of mediating translational repression. 24 It will be important to test the Y and H elements in vivo, by using transgenic mice.…”

Section: Regulatory Elements In the Mrnamentioning

confidence: 99%

See 2 more Smart Citations

Post–transcriptional control of gene expression during spermatogenesis

Braun

1998

Seminars in Cell & Developmental Biology

146

130

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Section: Activation Of Translationally Repressed Mrnassupporting

confidence: 61%

Section: Perspectivesmentioning

confidence: 99%

Section: Regulatory Elements In the Mrnamentioning

confidence: 99%

See 1 more Smart Citation

Post–transcriptional control of gene expression during spermatogenesis

Braun

1998

Seminars in Cell & Developmental Biology

146

130

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“…This sequence analysis revealed the presence of a strikingly conserved, bipartite recognition site (rBDNF CDS nucleotides 173-181 and 193-205; Fig. 2A), for the single stranded DNA/RNA binding protein translin, also known as testis brain-RNA binding protein (TB-RBP) (14,15). These two elements are 70% and 80% identical to the rat Protamine-2 Y' and H' elements, respectively.…”

Section: Differential Localization Of Bdnf Isoformsmentioning

confidence: 99%

Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation

Chiaruttini

Vicario

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

202

229

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Alternatively spliced brain-derived neurotrophic factor (BDNF) transcripts are targeted to distinct cellular compartments in neurons but the mechanisms underlying this sorting are unknown. Although only some BDNF isoforms are targeted to dendrites, we have found that the coding region common to all BDNF transcripts contains a constitutively active dendritic targeting signal and that this signal is suppressed in transcripts containing exons 1 or 4, which are restricted to the cell soma and proximal dendrites. This dendritic targeting signal is mediated by translin, an RNA-binding protein implicated in RNA trafficking, and is disrupted by the G196A mutation associated with memory deficits and psychiatric disorders. Molecular modeling and mutational studies indicate that the G196A mutation blocks dendritic targeting of BDNF mRNA by disrupting its interaction with translin. These findings implicate abnormal dendritic trafficking of BDNF mRNA in the pathophysiology of neuropsychiatric disorders linked to the G196A mutation.neuropsychiatric disorders ͉ neurotrophins S everal lines of evidence indicate that targeting of BDNF mRNA to dendrites plays a key role in mediating synaptic plasticity (1-4). However, the molecular mechanisms regulating this process and the differential subcellular localization of alternatively spliced BDNF transcripts, remain to be clarified.Multiple BDNF transcripts are generated by alternative splicing of one 5Ј exon with a shared 3Ј exon containing the entire BDNF coding region and either a short or long 3Ј UTR sequence (5, 6). In recent studies, we have demonstrated that BDNF transcripts differ in their subcellular localization (7). Exon 1 and 4 transcripts are localized in the cell soma, while exon 2 and 6 transcripts show a somato-dendritic localization. Thus, splice variants appear to encode spatial localization signals used to preferentially regulate BDNF expression in different subcellular domains (2, 3). A recent study has suggested that the long 3Ј UTR contains signals necessary for dendritic targeting of BDNF transcripts (4). However, it is unlikely that this mechanism can fully account for the differential dendritic targeting displayed by BDNF transcripts because more than one-third of exon 4 transcripts, which are retained in the soma, contain the long 3Ј UTR. Conversely, more than one-half of exon 6 transcripts, an isoform that displays targeting to dendrites, contain the short 3Ј UTR. To help define the mechanisms underlying differential localization of BDNF transcripts, we have tested the hypothesis that additional signals might be encoded by other BDNF mRNA regions.

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“…The human protein Translin and its mouse orthologue, testis-brain RNA-binding protein (TB-RBP), 1 are single-stranded DNA-and RNA-binding proteins with proposed functions in chromosomal translocations in lymphoid cells and mRNA transport and storage in brain and testis (1)(2)(3)(4). TB-RBP is a highly conserved protein with mouse and human proteins differing in 3 of 228 amino acids (5,6).…”

mentioning

confidence: 99%

Translin-associated Factor X Is Post-transcriptionally Regulated by Its Partner Protein TB-RBP, and Both Are Essential for Normal Cell Proliferation

Yang

Cho

Chennathukuzhi

et al. 2004

Journal of Biological Chemistry

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slow cell growth rates. We conclude that TRAX is posttranscriptionally stabilized by TB-RBP and both proteins are needed for normal cell proliferation.The human protein Translin and its mouse orthologue, testis-brain RNA-binding protein (TB-RBP), 1 are single-stranded DNA-and RNA-binding proteins with proposed functions in chromosomal translocations in lymphoid cells and mRNA transport and storage in brain and testis (1-4). TB-RBP is a highly conserved protein with mouse and human proteins differing in 3 of 228 amino acids (5, 6). In in vitro assays, TB-RBP/Translin binds to consensus chromosomal DNA breakpoint junctions as an octameric ring and recognizes DNA breaks at genomic hotspots (2,7,8). TB-RBP also binds to consensus RNA sequences present in many brain and testis mRNAs (6, 9 -11) and links specific mRNAs to microtubules (10,12,13). In the testis TB-RBP forms a complex with the Ter ATPase to transport specific mRNAs from nuclei to cytoplasm and through intercellular bridges (4). This ribonucleoprotein complex contains the kinesin KIF 17b, a testicular motor protein controlling transcription of CREM-regulated male germ cell mRNAs (14). The level of Translin has been demonstrated to closely parallel the proliferative state of somatic cells with its induced overexpression in HEK 293 cells accelerating cell proliferation (15). TRAX, first characterized as a Translin-like protein (16), forms DNA and RNA binding complexes with Translin (17,18). TRAX has been proposed to function in DNA repair in conjunction with the nuclear matrix protein C1D (19).Recently, we generated mice with a functional deletion of the TB-RBP gene (20). The mice are growth retarded and show defects in behavior and fertility. Many of the germ cells in the testis cannot proceed beyond first meiotic metaphase suggesting a defect in chromosome segregation and cytokinesis. Using 14.5-day-old embryos from heterozygous crosses, we have developed lines of MEFs from TB-RBP null animals and from their littermates. As in TB-RBP-deficient mice, these cells lack both TB-RBP and TRAX, although TRAX mRNA levels are not reduced. We find that early passage null MEFs have slower rates of proliferation with a block in the G 2 stage of the cell cycle. Reintroduction of TB-RBP increases the rate of cell proliferation and stabilizes the TRAX protein. Transgenic and transfection experiments indicate that TRAX protein is dependent upon TB-RBP for stabilization and both TB-RBP and TRAX are needed for normal cell proliferation. EXPERIMENTAL PROCEDURES Generation of MEFs-TB-RBP-deficientMEFs were derived from TB-RBP null mice generated by gene trapping (20). MEFs were produced using established protocols (21). Briefly, embryos were removed from pregnant heterozygous mice at 14.5 days and rinsed separately in sterile PBS. Fetal membranes, placenta, head, and soft tissues were discarded, and the remaining tissues were rinsed in fresh PBS. Each embryo was minced and incubated at 37°C for 5 min in 2 ml of 0.25% trypsin/EDTA. Debris was removed by passing the cell susp...

show abstract

Binding of a phosphoprotein to the 3' untranslated region of the mouse protamine 2 mRNA temporally represses its translation.

Cited by 151 publications

References 60 publications

Post–transcriptional control of gene expression during spermatogenesis

Post–transcriptional control of gene expression during spermatogenesis

Dendritic trafficking of BDNF mRNA is mediated by translin and blocked by the G196A (Val66Met) mutation

Translin-associated Factor X Is Post-transcriptionally Regulated by Its Partner Protein TB-RBP, and Both Are Essential for Normal Cell Proliferation

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