scholarly journals Human hTM alpha gene: expression in muscle and nonmuscle tissue.

1988 ◽  
Vol 8 (1) ◽  
pp. 433-440 ◽  
Author(s):  
A R MacLeod ◽  
C Gooding
Keyword(s):  
Skeletal Muscle ◽  
Human Fibroblasts ◽  
Mrna Splicing ◽  
Muscle Type ◽  
Gene Encoding ◽  
Protein Coding ◽  
Alternative Mrna Splicing ◽  
Cultured Human Fibroblasts ◽  
Alpha Gene ◽  
Complete Protein

We have isolated a cDNA clone from a human skeletal muscle library which contains the complete protein-coding sequence of a skeletal muscle alpha-tropomyosin. This cDNA sequence defines a fourth human tropomyosin gene, the hTM alpha gene, which is distinct from the hTMnm gene encoding a closely related isoform of skeletal muscle alpha-tropomyosin. In cultured human fibroblasts, the hTM alpha gene encodes both skeletal-muscle- and smooth-muscle-type alpha-tropomyosins by using an alternative mRNA-splicing mechanism.

Human hTM alpha gene: expression in muscle and nonmuscle tissue

1988 ◽  
Vol 8 (1) ◽  
pp. 433-440
Author(s):  
A R MacLeod ◽  
C Gooding
Keyword(s):  
Skeletal Muscle ◽  
Human Fibroblasts ◽  
Mrna Splicing ◽  
Muscle Type ◽  
Gene Encoding ◽  
Protein Coding ◽  
Alternative Mrna Splicing ◽  
Cultured Human Fibroblasts ◽  
Alpha Gene ◽  
Complete Protein

We have isolated a cDNA clone from a human skeletal muscle library which contains the complete protein-coding sequence of a skeletal muscle alpha-tropomyosin. This cDNA sequence defines a fourth human tropomyosin gene, the hTM alpha gene, which is distinct from the hTMnm gene encoding a closely related isoform of skeletal muscle alpha-tropomyosin. In cultured human fibroblasts, the hTM alpha gene encodes both skeletal-muscle- and smooth-muscle-type alpha-tropomyosins by using an alternative mRNA-splicing mechanism.

scholarly journals Epigenetic Regulation of Alternative mRNA Splicing in Dilated Cardiomyopathy

2020 ◽  
Vol 9 (5) ◽  
pp. 1499 ◽  
Author(s):  
Weng-Tein Gi ◽  
Jan Haas ◽  
Farbod Sedaghat-Hamedani ◽  
Elham Kayvanpour ◽  
Rewati Tappu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Dilated Cardiomyopathy ◽  
Gene Expression Regulation ◽  
Strong Association ◽  
Mrna Splicing ◽  
Environment Interaction ◽  
Protein Coding ◽  
Genetic Imprinting ◽  
Non Coding Rna ◽  
Alternative Mrna Splicing

In recent years, the genetic architecture of dilated cardiomyopathy (DCM) has been more thoroughly elucidated. However, there is still insufficient knowledge on the modifiers and regulatory principles that lead to the failure of myocardial function. The current study investigates the association of epigenome-wide DNA methylation and alternative splicing, both of which are important regulatory principles in DCM. We analyzed screening and replication cohorts of cases and controls and identified distinct transcriptomic patterns in the myocardium that differ significantly, and we identified a strong association of intronic DNA methylation and flanking exons usage (p < 2 × 10−16). By combining differential exon usage (DEU) and differential methylation regions (DMR), we found a significant change of regulation in important sarcomeric and other DCM-associated pathways. Interestingly, inverse regulation of Titin antisense non-coding RNA transcript splicing and DNA methylation of a locus reciprocal to TTN substantiate these findings and indicate an additional role for non-protein-coding transcripts. In summary, this study highlights for the first time the close interrelationship between genetic imprinting by DNA methylation and the transport of this epigenetic information towards the dynamic mRNA splicing landscape. This expands our knowledge of the genome–environment interaction in DCM besides simple gene expression regulation.

Cloning and characterization of a cDNA encoding transformation-sensitive tropomyosin isoform 3 from tumorigenic human fibroblasts

1988 ◽  
Vol 8 (1) ◽  
pp. 160-168
Author(s):  
C S Lin ◽  
J Leavitt
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Smooth Muscle ◽  
Rna Splicing ◽  
Human Fibroblasts ◽  
Fibroblast Cell ◽  
Coding Region ◽  
Base Pairs ◽  
Protein Coding ◽  
Peptide Length

We isolated a cDNA clone from the tumorigenic human fibroblast cell line HuT-14 that contains the entire protein coding region of tropomyosin isoform 3 (Tm3) and 781 base pairs of 5'- and 3'-untranslated sequences. Tm3, despite its apparent smaller molecular weight than Tm1 in two-dimensional gels, has the same peptide length as Tm1 (284 amino acids) and shares 83% homology with Tm1. Tm3 cDNA hybridized to an abundant mRNA of 1.3 kilobases in fetal muscle and cardiac muscle, suggesting that Tm3 is related to an alpha fast-tropomyosin. The first 188 amino acids of Tm3 are identical to those of rat or rabbit skeletal muscle alpha-tropomyosin, and the last 71 amino acids differ from those of rat smooth muscle alpha-tropomyosin by only 1 residue. Tm3 therefore appears to be encoded by the same gene that encodes the fast skeletal muscle alpha-tropomyosin and the smooth muscle alpha-tropomyosin via an alternative RNA-splicing mechanism. In contrast to Tm4 and Tm5, Tm3 has a small gene family, with, at best, only one pseudogene.

Isolation and characterization of related cDNA clones encoding skeletal muscle beta-tropomyosin and a low-molecular-weight nonmuscle tropomyosin isoform

1989 ◽  
Vol 9 (1) ◽  
pp. 185-192
Author(s):  
J A Bradac ◽  
C E Gruber ◽  
S Forry-Schaudies ◽  
S H Hughes
Keyword(s):  
Skeletal Muscle ◽  
Molecular Weight ◽  
Amino Acid ◽  
Cdna Library ◽  
Low Molecular Weight ◽  
Cdna Clones ◽  
Protein Coding ◽  
Coding Sequence ◽  
Untranslated Sequence ◽  
Complete Protein

We have isolated and characterized cDNA clones from chicken cDNA libraries derived from skeletal muscle, body wall, and cultured fibroblasts. A clone isolated from a skeletal muscle cDNA library contains the complete protein-coding sequence of the 284-amino-acid skeletal muscle beta-tropomyosin together with 72 bases of 5' untranslated sequence and nearly the entire 3' untranslated region (about 660 bases), lacking only the last 4 bases and the poly(A) tail. A second clone, isolated from the fibroblast cDNA library, contains the complete protein-coding sequence of a 248-amino-acid fibroblast tropomyosin together with 77 bases of 5' untranslated sequence and 235 bases of 3' untranslated sequence through the poly(A) tract. The derived amino acid sequence from this clone exhibits only 82% homology with rat fibroblast tropomyosin 4 and 80% homology with human fibroblast tropomyosin TM30nm, indicating that this clone encodes a third 248-amino-acid tropomyosin isoform class. The protein product of this mRNA is fibroblast tropomyosin 3b, one of two low-molecular-weight isoforms expressed in chicken fibroblast cultures. Comparing the sequences of the skeletal muscle and fibroblast cDNAs with a previously characterized clone which encodes the smooth muscle alpha-tropomyosin reveals two regions of absolute homology, suggesting that these three clones were derived from the same gene by alternative RNA splicing.

scholarly journals Tissue-specific alternative splicing of protein 4.1 inserts an exon necessary for formation of the ternary complex with erythrocyte spectrin and F-actin

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2558-2563 ◽  
Author(s):  
WC Horne ◽  
SC Huang ◽  
PS Becker ◽  
TK Tang ◽  
EJ Jr Benz
Keyword(s):  
Ternary Complex ◽  
Mrna Splicing ◽  
Actin Binding ◽  
Protein 4.1 ◽  
Alternative Mrna Splicing ◽  
Actin Binding Domain ◽  
Peripheral Membrane Protein ◽  
Specific Alternative ◽  
Erythroid Maturation ◽  
Complete Protein

Abstract Erythrocyte protein 4.1 is an 78- to 80-Kd peripheral membrane protein that promotes the interaction of spectrin with actin protofilaments and links the resulting interlocking network to the integral membrane proteins. There are several isoforms of protein 4.1 that appear to be expressed in a restricted group of tissues. These arise from alternative mRNA splicing events that lead to the combinational insertion or deletion of at least 10 blocks of nucleotides (motifs) within the mature mRNA. One of these, motif I, consists of 63 nucleotides encoding 21 amino acids in the N-terminal region of the putative spectrin/actin-binding domain. The expression of the motif U- containing isoform occurs late in erythroid maturation. We generated recombinant isoforms of protein 4.1 and of the putative 10-Kd spectrin/actin-binding fragment that contain or lack this 21 amino acid sequence and examined their ability to form a ternary complex with erythrocyte spectrin and F-actin. The isoforms of the complete protein and of the 10-Kd fragment that contain the sequence encoded by motif I efficiently form the ternary complex. Isoforms that lack this sequence, but are otherwise identical, do not participate in the formation of the ternary complex. These results, in conjunction with the expression of motif I during late erythroid maturation, suggest that interaction with actin and the erythroid form of spectrin is a specialized property of the erythrocyte form of protein 4.1. Alternative mRNA splicing in developing red blood cells thus plays a key adaptive role in the formation of the highly specialized erythrocyte membrane.

scholarly journals Tissue-specific alternative splicing of protein 4.1 inserts an exon necessary for formation of the ternary complex with erythrocyte spectrin and F-actin

Blood ◽  
1993 ◽  
Vol 82 (8) ◽  
pp. 2558-2563 ◽  
Author(s):  
WC Horne ◽  
SC Huang ◽  
PS Becker ◽  
TK Tang ◽  
EJ Jr Benz
Keyword(s):  
Ternary Complex ◽  
Mrna Splicing ◽  
Actin Binding ◽  
Protein 4.1 ◽  
Alternative Mrna Splicing ◽  
Actin Binding Domain ◽  
Peripheral Membrane Protein ◽  
Specific Alternative ◽  
Erythroid Maturation ◽  
Complete Protein

Erythrocyte protein 4.1 is an 78- to 80-Kd peripheral membrane protein that promotes the interaction of spectrin with actin protofilaments and links the resulting interlocking network to the integral membrane proteins. There are several isoforms of protein 4.1 that appear to be expressed in a restricted group of tissues. These arise from alternative mRNA splicing events that lead to the combinational insertion or deletion of at least 10 blocks of nucleotides (motifs) within the mature mRNA. One of these, motif I, consists of 63 nucleotides encoding 21 amino acids in the N-terminal region of the putative spectrin/actin-binding domain. The expression of the motif U- containing isoform occurs late in erythroid maturation. We generated recombinant isoforms of protein 4.1 and of the putative 10-Kd spectrin/actin-binding fragment that contain or lack this 21 amino acid sequence and examined their ability to form a ternary complex with erythrocyte spectrin and F-actin. The isoforms of the complete protein and of the 10-Kd fragment that contain the sequence encoded by motif I efficiently form the ternary complex. Isoforms that lack this sequence, but are otherwise identical, do not participate in the formation of the ternary complex. These results, in conjunction with the expression of motif I during late erythroid maturation, suggest that interaction with actin and the erythroid form of spectrin is a specialized property of the erythrocyte form of protein 4.1. Alternative mRNA splicing in developing red blood cells thus plays a key adaptive role in the formation of the highly specialized erythrocyte membrane.

scholarly journals Cloning and characterization of a cDNA encoding transformation-sensitive tropomyosin isoform 3 from tumorigenic human fibroblasts.

1988 ◽  
Vol 8 (1) ◽  
pp. 160-168 ◽  
Author(s):  
C S Lin ◽  
J Leavitt
Keyword(s):  
Skeletal Muscle ◽  
Amino Acids ◽  
Smooth Muscle ◽  
Rna Splicing ◽  
Human Fibroblasts ◽  
Fibroblast Cell ◽  
Coding Region ◽  
Base Pairs ◽  
Protein Coding ◽  
Peptide Length

We isolated a cDNA clone from the tumorigenic human fibroblast cell line HuT-14 that contains the entire protein coding region of tropomyosin isoform 3 (Tm3) and 781 base pairs of 5'- and 3'-untranslated sequences. Tm3, despite its apparent smaller molecular weight than Tm1 in two-dimensional gels, has the same peptide length as Tm1 (284 amino acids) and shares 83% homology with Tm1. Tm3 cDNA hybridized to an abundant mRNA of 1.3 kilobases in fetal muscle and cardiac muscle, suggesting that Tm3 is related to an alpha fast-tropomyosin. The first 188 amino acids of Tm3 are identical to those of rat or rabbit skeletal muscle alpha-tropomyosin, and the last 71 amino acids differ from those of rat smooth muscle alpha-tropomyosin by only 1 residue. Tm3 therefore appears to be encoded by the same gene that encodes the fast skeletal muscle alpha-tropomyosin and the smooth muscle alpha-tropomyosin via an alternative RNA-splicing mechanism. In contrast to Tm4 and Tm5, Tm3 has a small gene family, with, at best, only one pseudogene.

scholarly journals Isolation and characterization of related cDNA clones encoding skeletal muscle beta-tropomyosin and a low-molecular-weight nonmuscle tropomyosin isoform.

1989 ◽  
Vol 9 (1) ◽  
pp. 185-192 ◽  
Author(s):  
J A Bradac ◽  
C E Gruber ◽  
S Forry-Schaudies ◽  
S H Hughes
Keyword(s):  
Skeletal Muscle ◽  
Molecular Weight ◽  
Amino Acid ◽  
Cdna Library ◽  
Low Molecular Weight ◽  
Cdna Clones ◽  
Protein Coding ◽  
Coding Sequence ◽  
Untranslated Sequence ◽  
Complete Protein

We have isolated and characterized cDNA clones from chicken cDNA libraries derived from skeletal muscle, body wall, and cultured fibroblasts. A clone isolated from a skeletal muscle cDNA library contains the complete protein-coding sequence of the 284-amino-acid skeletal muscle beta-tropomyosin together with 72 bases of 5' untranslated sequence and nearly the entire 3' untranslated region (about 660 bases), lacking only the last 4 bases and the poly(A) tail. A second clone, isolated from the fibroblast cDNA library, contains the complete protein-coding sequence of a 248-amino-acid fibroblast tropomyosin together with 77 bases of 5' untranslated sequence and 235 bases of 3' untranslated sequence through the poly(A) tract. The derived amino acid sequence from this clone exhibits only 82% homology with rat fibroblast tropomyosin 4 and 80% homology with human fibroblast tropomyosin TM30nm, indicating that this clone encodes a third 248-amino-acid tropomyosin isoform class. The protein product of this mRNA is fibroblast tropomyosin 3b, one of two low-molecular-weight isoforms expressed in chicken fibroblast cultures. Comparing the sequences of the skeletal muscle and fibroblast cDNAs with a previously characterized clone which encodes the smooth muscle alpha-tropomyosin reveals two regions of absolute homology, suggesting that these three clones were derived from the same gene by alternative RNA splicing.

Slow skeletal muscle myosin-binding protein-C (MyBPC1) mediates recruitment of muscle-type creatine kinase (CK) to myosin

2011 ◽  
Vol 436 (2) ◽  
pp. 437-445 ◽  
Author(s):  
Zhe Chen ◽  
Tong-Jin Zhao ◽  
Jie Li ◽  
Yan-Song Gao ◽  
Fan-Guo Meng ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Creatine Kinase ◽  
Muscle Contraction ◽  
Binding Protein ◽  
High Energy ◽  
Functional Coupling ◽  
Muscle Type ◽  
Myosin Binding Protein ◽  
Slow Skeletal Muscle ◽  
Myosin Binding

Muscle contraction requires high energy fluxes, which are supplied by MM-CK (muscle-type creatine kinase) which couples to the myofibril. However, little is known about the detailed molecular mechanisms of how MM-CK participates in and is regulated during muscle contraction. In the present study, MM-CK is found to physically interact with the slow skeletal muscle-type MyBPC1 (myosin-binding protein C1). The interaction between MyBPC1 and MM-CK depended on the creatine concentration in a dose-dependent manner, but not on ATP, ADP or phosphocreatine. The MyBPC1–CK interaction favoured acidic conditions, and the two molecules dissociated at above pH 7.5. Domain-mapping experiments indicated that MM-CK binds to the C-terminal domains of MyBPC1, which is also the binding site of myosin. The functional coupling of myosin, MyBPC1 and MM-CK is further corroborated using an ATPase activity assay in which ATP expenditure accelerates upon the association of the three proteins, and the apparent Km value of myosin is therefore reduced. The results of the present study suggest that MyBPC1 acts as an adaptor to connect the ATP consumer (myosin) and the regenerator (MM-CK) for efficient energy metabolism and homoeostasis.

scholarly journals Influence of chlorate on proteoglycan biosynthesis by cultured human fibroblasts.

1988 ◽  
Vol 263 (26) ◽  
pp. 12886-12892 ◽  
Author(s):  
H Greve ◽  
Z Cully ◽  
P Blumberg ◽  
H Kresse
Keyword(s):  
Human Fibroblasts ◽  
Cultured Human Fibroblasts
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