Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skeletal muscle beta-tropomyosin, smooth muscle alpha-tropomyosin, and a low molecular weight fibroblast tropomyosin are generated by alternatively splicing RNA transcripts of the chicken tropomyosin 1 (TM 1) gene (Forry-Schaudies, S., Maihle, N. J., and Hughes, S. H. (1990) J. Mol. Biol. 211; 321-330). Two novel tropomyosin cDNAs that derive from mRNAs of the TM 1 gene have been isolated from a chicken embryo brain cDNA library. Brain cDNA BRT-1 is 2.2 kilobases in length and encodes 283 amino acids. It is identical to skeletal muscle beta-tropomyosin from amino acids 1 to 258. The sequence 3' of this point is unique to BRT-1; a comparison to genomic sequence indicates that a new carboxyl-terminal exon is used to generate this sequence. 1.4-kilobase brain cDNA BRT-2 contains sequences found in both fibroblast cDNA FT-beta (5'-end) and skeletal muscle cDNA SKT-beta (3'-end). RNase and S1 nuclease assays using RNA samples from leg muscle, gizzard, fibroblasts, and brain indicate that the TM 1 gene expresses four additional tropomyosin RNAs by alternately splicing previously characterized exons. These results demonstrate that the chicken TM 1 gene encodes nine tropomyosin RNAs through the use of two promoters, two internal exons that are mutually exclusive, and three 3'-exons. Implications for the regulation of alternative splicing are discussed.
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PMID:The chicken tropomyosin 1 gene generates nine mRNAs by alternative splicing. 185 15

A full-length cDNA clone coding for a 248-amino-acid tropomyosin (TM) was isolated from a Xenopus laevis (Xl) oocyte cDNA library. This TM is very similar to the members of the non-muscle (nm) TM family that includes rat TM-4, human TM30pl and chicken cardiac fibroblast FT-C. An RNase protection assay showed that the corresponding transcript is expressed ubiquitously and revealed the presence of an alternative transcript in adult heart RNA. A full-length cDNA clone was isolated from an adult heart cDNA library using a nm TM-encoding cDNA probe. It encodes a muscle TM homologous to chicken FT-C and the corresponding mRNA is expressed in adult RNA and to a very low level in adult skeletal muscle. The two cDNAs correspond to two alternatively spliced isoforms of TM generated from the Xl TM-4 gene. These data, together with published observations, demonstrated that, in this amphibian, the cardiac muscle TM are synthesized from the TM alpha and TM-4 genes.
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PMID:The Xenopus laevis TM-4 gene encodes non-muscle and cardiac tropomyosin isoforms through alternative splicing. 775 66

Previous studies have shown that three distinct genes encode six isoforms of tropomyosin (TM) in rat fibroblasts: the alpha gene encodes TM-2, TM-3, TM-5a, and TM-5b, the beta gene encodes TM-1, and the TM-4 gene encodes TM-4. Here we report the characterization of a cDNA clone encoding the most recent rat fibroblast TM to be identified, herein referred to as TM-5, that is the product of a fourth gene that is homologous to the human hTMnm gene, herein referred to as the rat slow-twitch alpha TM gene. The cDNA clone is approximately 1.7 kb and encodes a protein of 248 amino acids. Using two-dimensional gel electrophoresis, the TM-5 protein was found to co-migrate with fibroblast TM-5a and 5b. Comparison of the amino acid sequences of TM-5 to other fibroblast isoforms encoded by the alpha, beta, and TM-4 genes revealed a high degree of homology, although there were regions of divergence among the different isoforms. The gene encoding TM-5 is expressed in all tissues examined including skeletal muscle, stomach, heart, liver, kidney, uterus, spleen, brain, and diaphragm. However, Northern blot and RNase protection analyses revealed the presence of different mRNAs in fibroblasts, striated muscle (skeletal and diaphragm), and brain, which are expressed via alternative RNA splicing and the use of alternative promoters. The TM-5 protein was expressed in a bacterial system and tested for its ability to bind actin in vitro and in vivo. The apparent TM association constant (Ka) was taken as the free concentration at half saturation and was found to be 3 microM for TM-5 compared to 2 microM for TM-5b at an F-actin concentration of 42 microM. When fluorescently-labeled TM-5 was microinjected into living rat fibroblasts, it localized to the stress fibers and ruffles of the leading lamella. The coiled-coil interactions of TM-5 with other low and high molecular weight TM isoforms were studied. TM-5 and TM-4 were capable of dimerizing with each other as well as with other low molecular weight isoforms (TM-5a and TM-5b), but not with the HMW isoforms (TM-1, TM-2, and TM-3). In addition, TM-5a and TM-5b were unable to heterodimerize with each other. The implications of these results in understanding the role of TM diversity in cytoskeletal dynamics are discussed.
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PMID:Low molecular weight rat fibroblast tropomyosin 5 (TM-5): cDNA cloning, actin-binding, localization, and coiled-coil interactions. 867 41

Tropomodulin is a 40.6-kDa isoform-specific tropomyosin-binding protein which inhibits actin filament elongation from the slow-growing (pointed) end and localizes at or near the pointed ends of thin filaments in rat skeletal muscle. Immunofluorescent localization using affinity-purified anti-tropomodulin antibodies in avian myofibril preparations demonstrates novel immunoreactivity at the Z-disc in addition to the previously reported localization at the periphery of I-Z-I brushes where actin filaments terminate. Identical results were obtained using antibody preparations generated against either bacterially expressed tropomodulin or human erythrocyte tropomodulin. Chicken muscle preparations contain Mr 43000 polypeptides which bind antibodies generated against tropomodulin in Western blot analysis, as well as 125I-labeled tropomyosin in blot overlays. Tropomodulin mRNA expression in adult muscle was confirmed by RNase protection assays, and the sequence of our tropomodulin cDNA amplified from chicken muscle mRNA preparations by polymerase chain reaction closely matches clones selected by chicken muscle cDNA library screening. The novel immunolocalization we report raises new possibilities for the role of tropomodulin in the organization of avian skeletal muscle at the Z-disc. We conclude that tropomodulin is likely to be important in striated muscle biology as a structural component in the Z-disc region which participates in the process of thin filament organization and assembly.
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PMID:Chicken skeletal muscle tropomodulin: novel localization and characterization. 876 65

We have identified and characterized two proteins in rat brain that bind to the neuron-specific tropomyosin isoform, TMBr3. The two proteins were identified by blot overlay assay, in which the proteins immobilized on the membrane were probed by epitope-tagged TMBr3, followed by detection with anti-epitope antibody. We have purified these proteins using a TMBr3 affinity column. Peptide sequencing as well as immunoblotting showed that one of the two proteins is identical to tropomodulin, a tropomyosin-binding protein originally identified in erythrocytes. The cDNA for the other protein was cloned from an adult rat brain cDNA library using degenerate oligonucleotides that we designed based on the peptide sequences. Sequence analysis of the cDNA clone revealed this protein to be a novel isoform of tropomodulin which is the product of a distinct gene, and is herein referred to as N-tropomodulin. Recombinant N-tropomodulin bound to TMBr3 as well as to other low molecular mass tropomyosins (TM5a or TM5), but not to high molecular mass tropomyosins (TM2 or TMBr1). Northern blotting and RNase protection assays as well as immunoblotting showed that N-tropomodulin is expressed predominantly in brain. Furthermore, RNase protection assays revealed no alternatively spliced regions within the coding sequence. Developmentally, N-tropomodulin was detected in rat brain as early as embryonic day 14 and reaches the adult level before birth. Immunofluorescence of primary frontal cortex cell cultures showed that N-tropomodulin is specifically expressed in neurons. The neuron-specific expression of N-tropomodulin strongly suggests specialized roles of this TM-binding protein in neurons.
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PMID:N-tropomodulin: a novel isoform of tropomodulin identified as the major binding protein to brain tropomyosin. 888 80

Previous studies of the tropomyosin-alpha gene using Northern blot and ribonuclease protection assay methods identified the expression of nine isoforms generated by alternative splicing of exons. Several of these isoforms were characterized as tissue-specific and/or developmentally specific. The present study used a highly sensitive RT-PCR-based strategy to assay the expression of these and many novel isoforms in a variety of adult rat tissues. All 9 isoforms were found to be expressed in all tissues evaluated. Furthermore, 20 new isoforms were identified with varying tissue specificity. Sequence analysis confirmed exon splicing patterns. This greater degree of isoform generation parallels recent findings for another tropomyosin gene, the TM-5 gene, for which the generation of new isoforms, in particular, ones using novel junctions for carboxy-terminal-coding exons, was also shown. Several of the new cDNA-based isoforms predict tropomyosin protein species that are 10 amino acids longer than previously characterized high-molecular-weight tropomyosin-alpha gene isoforms. The apparent lack of significant tissue specificity in the expression of tropomyosin isoforms suggests that many of these isoforms have more generic roles in cell function.
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PMID:Multiple combinations of alternatively spliced exons in rat tropomyosin-alpha gene mRNA: evidence for 20 new isoforms in adult tissues and cultured cells. 1136 17