scholarly journals Structure and Sequence of the Human Fast Skeletal Troponin T (TNNT3) Gene: Insight Into the Evolution of the Gene and the Origin of the Developmentally Regulated Isoforms

2003 ◽  
Vol 4 (6) ◽  
pp. 609-625 ◽  
Author(s):  
Raymund Stefancsik ◽  
Jeffrey D. Randall ◽  
Chengjian Mao ◽  
Satyapriya Sarkar
Keyword(s):  
Evolutionary Dynamics ◽  
Troponin I ◽  
Troponin T ◽  
Protein Isoforms ◽  
Heptad Repeat ◽  
Coding Region ◽  
Developmentally Regulated ◽  
Ancestral Gene ◽  
Alternatively Spliced ◽  
Alternatively Spliced Exons

We describe the cloning, sequencing and structure of the human fast skeletal troponin T (TNNT3) gene located on chromosome 11p15.5. The single-copy gene encodes 19 exons and 18 introns. Eleven of these exons, 1–3, 9–15 and 18, are constitutively spliced, whereas exons 4–8 are alternatively spliced. The gene contains an additional subset of developmentally regulated and alternatively spliced exons, including a foetal exon located between exon 8 and 9 and exon 16 or α (adult) and 17 or β (foetal and neonatal). Exon phasing suggests that the majority of the alternatively spliced exons located at the 5′ end of the gene may have evolved as a result of exon shuffling, because they are of the same phase class. In contrast, the 3′ exons encoding an evolutionarily conserved heptad repeat domain, shared by both TnT and troponin I (TnI), may be remnants of an ancient ancestral gene. The sequence of the 5′ flanking region shows that the putative promoter contains motifs including binding sites for MyoD, MEF-2 and several transcription factors which may play a role in transcriptional regulation and tissue-specific expression of TnT. The coding region of TNNT3 exhibits strong similarity to the corresponding rat sequence. However, unlike the rat TnT gene, TNNT3 possesses two repeat regions of CCA and TC. The exclusive presence of these repetitive elements in the human gene indicates divergence in the evolutionary dynamics of mammalian TnT genes. Homologous muscle-specific splicing enhancer motifs are present in the introns upstream and downstream of the foetal exon, and may play a role in the developmental pattern of alternative splicing of the gene. The genomic correlates of TNNT3 are relevant to our understanding of the evolution and regulation of expression of the gene, as well as the structure and function of the protein isoforms. The nucleotide sequence of TNNT3 has been submitted to EMBL/GenBank under Accession No. AF026276.

Novel developmentally regulated exon identified in the rat fast skeletal muscle troponin T gene

1993 ◽  
Vol 106 (3) ◽  
pp. 903-908 ◽  
Author(s):  
M.J. Morgan ◽  
J.C. Earnshaw ◽  
G.K. Dhoot
Keyword(s):  
Skeletal Muscle ◽  
Troponin T ◽  
Fast Skeletal Muscle ◽  
Mrna Isoforms ◽  
Developmentally Regulated ◽  
Adult Skeletal Muscle ◽  
Alternatively Spliced ◽  
Molecular Masses ◽  
First Time ◽  
Alternatively Spliced Exons

In theory, the rat fast skeletal muscle troponin T gene can generate 64 different isoforms. Here we report the identification of a novel alternative exon (exon y) that increases the potential isoform variation to 128. The inclusion of exon y in fast skeletal muscle troponin T mRNA occurs in perinatal, but not adult, skeletal muscle. Exon y is located between exons 8 and 9. This is the first time that a developmentally regulated exon located amongst a set of alternatively spliced exons has been described. Exon y is included in two mRNA isoforms. The proteins that these mRNAs would encode have molecular masses greater than that of the largest fast skeletal muscle troponin T isoform lacking exon y. These two proteins correlate well in both size and pattern of expression with the two fast skeletal muscle troponin T isoforms expressed in perinatal skeletal muscle. These results indicate that there is coordinated regulation of the splicing of exon y with other alternative exons.

scholarly journals Influence of Intron Length on Alternative Splicing of CD44

1998 ◽  
Vol 18 (10) ◽  
pp. 5930-5941 ◽  
Author(s):  
Martyn V. Bell ◽  
Alison E. Cowper ◽  
Marie-Paule Lefranc ◽  
John I. Bell ◽  
Gavin R. Screaton
Keyword(s):  
Alternative Splicing ◽  
Genomic Structure ◽  
Single Gene ◽  
Intron Length ◽  
Protein Isoforms ◽  
Major Influence ◽  
Eukaryotic Genes ◽  
Alternatively Spliced ◽  
Alternatively Spliced Exons

ABSTRACT Although the splicing of transcripts from most eukaryotic genes occurs in a constitutive fashion, some genes can undergo a process of alternative splicing. This is a genetically economical process which allows a single gene to give rise to several protein isoforms by the inclusion or exclusion of sequences into or from the mature mRNA. CD44 provides a unique example; more than 1,000 possible isoforms can be produced by the inclusion or exclusion of a central tandem array of 10 alternatively spliced exons. Certain alternatively spliced exons have been ascribed specific functions; however, independent regulation of the inclusion or skipping of each of these exons would clearly demand an extremely complex regulatory network. Such a network would involve the interaction of many exon-specific trans-acting factors with the pre-mRNA. Therefore, to assess whether the exons are indeed independently regulated, we have examined the alternative exon content of a large number of individual CD44 cDNA isoforms. This analysis shows that the downstream alternatively spliced exons are favored over those lying upstream and that alternative exons are often included in blocks rather than singly. Using a novel in vivo alternative splicing assay, we show that intron length has a major influence upon the alternative splicing of CD44. We propose a kinetic model in which short introns may overcome the poor recognition of alternatively spliced exons. These observations suggest that for CD44, intron length has been exploited in the evolution of the genomic structure to enable tissue-specific patterns of splicing to be maintained.

Temperature and developmental plasticity of muscle phenotype in herring larvae

1997 ◽  
Vol 200 (5) ◽  
pp. 849-868 ◽  
Author(s):  
I A Johnston ◽  
N J Cole ◽  
V L A Vieira ◽  
I Davidson
Keyword(s):  
Developmental Plasticity ◽  
Troponin I ◽  
Troponin T ◽  
Clupea Harengus ◽  
Protein Isoforms ◽  
Muscle Fibres ◽  
Larval Stages ◽  
Somite Stage ◽  
Horizontal Septum ◽  
Red Muscle

Myogenesis, the expression of myofibrillar protein isoforms and the development of muscle innervation were investigated in Clyde herring (Clupea harengus L.) in two successive spawning seasons at temperatures ranging from 5 °C to 15 °C. Myotube formation occurred in a rostral to caudal progression at similar somite stages at all temperatures. Superficial mononuclear muscle pioneer fibres were present at the horizontal septum. Myofibrillogenesis was retarded with respect to somite stage at low temperatures; for example, by the 50-somite stage, myofibrils were observed in the muscle pioneers of the first 31 somites at 12 °C, but only the first 20 somites at 5 °C. In the electron microscope, the earliest stages of myofibril assembly were observed in the muscle pioneer cells and in a proportion of the multinucleated myotubes within the same somite. By the end of somitogenesis, the density of myofibrils in the rostral myotomes was much higher at 15 °C than at 5 °C. Embryonic isoforms of myosin light chain 2 (LC2), troponin I and troponin T were identified in the presumptive white muscle using two-dimensional gel electrophoresis. Expression of the embryonic isoforms was gradually switched off during the larval stages. The size range over which embryonic isoforms were present was inversely related to rearing temperature. For example, the adult pattern of myosin LC2 expression was established at 11 mm total length (TL) at 15 °C, but not until 15 mm TL at 5 °C. Acetylcholinesterase staining was apparent at the myosepta in 31-somite stage embryos at 15 °C, but not until approximately the 40-somite stage at 5 °C. The red muscle fibres of larvae were initially innervated only at their myoseptal ends. The temperature at which the red muscle fibres became multiply innervated was inversely related to body size, occurring at 12­14 mm at 12 °C, but not until 16­19 mm at 5 °C. We conclude that the temperature during early development determines the relative timing and degree of expression of the myogenic programme, resulting in significant phenotypic variation in the swimming muscles of the larval stages. Our results highlight a potential mechanism whereby early thermal experience could influence survival and hence the strength of particular year classes of fish.

scholarly journals Differential regulation of myofilament protein isoforms underlying the contractility changes in skeletal muscle unloading

2007 ◽  
Vol 292 (3) ◽  
pp. C1192-C1203 ◽  
Author(s):  
Zhi Bin Yu ◽  
Fang Gao ◽  
Han Zhong Feng ◽  
Jian-Ping Jin
Keyword(s):  
Skeletal Muscle ◽  
Soleus Muscle ◽  
Troponin I ◽  
Troponin T ◽  
Weight Bearing ◽  
Regulatory Protein ◽  
Differential Regulation ◽  
Hindlimb Unloading ◽  
Protein Isoforms ◽  
Hindlimb Suspension

Weight-bearing skeletal muscles change phenotype in response to unloading. Using the hindlimb suspension rat model, we investigated the regulation of myofilament protein isoforms in correlation to contractility. Four weeks of continuous hindlimb unloading produced progressive atrophy and contractility changes in soleus but not extensor digitorum longus muscle. The unloaded soleus muscle also had decreased fatigue resistance. Along with the decrease of myosin heavy chain isoform I and IIa and increase of IIb and IIx, coordinated regulation of thin filament regulatory protein isoforms were observed: γ- and β-tropomyosin decreased and α-tropomyosin increased, resulting in an α/β ratio similar to that in normal fast twitch skeletal muscle; troponin I and troponin T (TnT) both showed decrease in the slow isoform and increases in the fast isoform. The TnT isoform switching began after 7 days of unloading and TnI isoform showed detectable changes at 14 days while other protein isoform changes were not significant until 28 days of treatment. Correlating to the early changes in contractility, especially the resistance to fatigue, the early response of TnT isoform regulation may play a unique role in the adaptation of skeletal muscle to unloading. When the fast TnT gene expression was upregulated in the unloaded soleus muscle, alternative RNA splicing switched to produce more high molecular weight acidic isoforms, reflecting a potential compensation for the decrease of slow TnT that is critical to skeletal muscle function. The results demonstrate that differential regulation of TnT isoforms is a sensitive mechanism in muscle adaptation to functional demands.

scholarly journals Evolutionary conservation of the structure and expression of alternatively spliced Ultrabithorax isoforms from Drosophila.

Genetics ◽  
1994 ◽  
Vol 136 (3) ◽  
pp. 965-977
Author(s):  
H M Bomze ◽  
A J López
Keyword(s):  
Alternative Splicing ◽  
Protein Function ◽  
Developmental Regulation ◽  
Expression Patterns ◽  
Proximal Region ◽  
Amino Acid Sequences ◽  
Drosophila Virilis ◽  
Protein Isoforms ◽  
Developmentally Regulated ◽  
Alternatively Spliced

Abstract In Drosophila melanogaster, alternatively spliced mRNAs from the homeotic gene Ultrabithorax (Ubx) encode a family of structurally distinct homeoprotein isoforms. The developmentally regulated expression patterns of these isoforms suggest that they have specialized stage- and tissue-specific functions. To evaluate the functional importance of UBX isoform diversity and gain clues to the mechanism that regulates processing of Ubx RNAs, we have investigated whether the Ubx RNAs of other insects undergo similar alternative splicing. We have isolated and characterized Ubx cDNA fragments from D. melanogaster, Drosophila pseudoobscura, Drosophila hydei and Drosophila virilis, species separated by as much as 60 million years of evolution, and have found that three aspects of Ubx RNA processing have been conserved. (1) These four species exhibit identical patterns of optional exon use in a region adjacent to the homeodomain. (2) These four species produce the same family of UBX protein isoforms with identical amino acid sequences in the optional exons, even though the common amino-proximal region has undergone substantial divergence. The nucleotide sequences of the optional exons, including third positions of rare codons, have also been conserved strongly, suggesting functional constraints that are not limited to coding potential. (3) The tissue- and stage-specific patterns of expression of different UBX isoforms are identical among these Drosophila species, indicating that the developmental regulation of the alternative splicing events has also been conserved. These findings argue for an important role of alternative splicing in Ubx function. We discuss the implications of these results for models of UBX protein function and the mechanism of alternative splicing.

Electrically silent potassium channel subunits from human lens epithelium

1999 ◽  
Vol 277 (3) ◽  
pp. C412-C424 ◽  
Author(s):  
Allan R. Shepard ◽  
James L. Rae
Keyword(s):  
Single Channel ◽  
Lens Epithelium ◽  
Human Lens ◽  
Hybrid Mapping ◽  
Coding Region ◽  
Channel Conductance ◽  
Alternatively Spliced ◽  
Human Lens Epithelium ◽  
Alternatively Spliced Exons

We describe the cloning and characterization of the first human members, hKv9.1 and hKv9.3, of the electrically silent delayed-rectifying-like K+channel subfamily. Their modulatory effects on the electrically active subfamily member hKv2.1 are also quantified. The hKv9 K+channels were isolated from a human lens epithelium cDNA library, but both hKv9.1 mRNA and hKv9.3 mRNA were found to coexist with the mRNA for hKv2.1 in a large number of human tissues. The hKv9.1 gene is composed of a minimum of five exons, with at least two alternatively spliced exons in the 5′-untranslated region (UTR). In contrast, the hKv9.3 gene is intronless across the coding region, 3′-UTR, and all of the analyzed 5′-UTR. Radiation hybrid mapping localized the hKv9.1 gene to 20q12 and the hKv9.3 gene to 2p24. Each electrically silent subunit, when coexpressed with hKv2.l, slows deactivation and inactivation compared with hKv2.1 expressed alone. In addition, each results in an increment in the single channel conductance.

1461-P: Cardiac Troponin T and Troponin I and Incident Diabetes in the General Population: Generation Scotland Scottish Family Health Study

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1461-P
Author(s):  
PAUL WELSH ◽  
DAVID PREISS ◽  
ARCHIE CAMPBELL ◽  
DAVID J. PORTEOUS ◽  
NICHOLAS L. MILLS ◽  
...  
Keyword(s):  
General Population ◽  
Cardiac Troponin ◽  
Troponin I ◽  
Troponin T ◽  
Family Health ◽  
Incident Diabetes ◽  
Health Study ◽  
Cardiac Troponin T ◽  
Generation Scotland

Postmortem Specificity of Troponin for Acute Miocard Infarction Diagnosis throug Qualitative Dosing from Pericardial Fluid

2018 ◽  
Vol 69 (9) ◽  
pp. 2482-2486
Author(s):  
Iuliana Hunea ◽  
Simona Irina Damian ◽  
Carmen Corina Radu ◽  
Sorin Moldoveanu ◽  
Tatiana Iov
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Disease ◽  
Cardiac Death ◽  
Troponin I ◽  
Troponin T ◽  
Morphological Changes ◽  
Pericardial Fluid ◽  
Histological Changes ◽  
Lethal Arrhythmia ◽  
Myocardial Lesions

Cardiac disease is the leading cause of death, and sudden cardiac death occupies the first place in sudden deaths of natural causes. Sudden cardiac death due to lethal arrhythmia may be the first manifestation of a cardiac disease, such cases becoming suspect dead, thus forensic cases. The autopsy performed in such cases may reveal important cardiovascular disease but not obvious macroscopic or histological changes of acute myocardial infarction (IMA), except for cases of survival for several hours after the onset of the symptomatology. Biochemical markers were used to test for myocardial lesions in the absence of morphological changes. Methods for determining myoglobin, CK-MB, troponin T (cTn T), troponin I (cTn I) were introduced to the clinic to diagnose the condition of patients with chest pain as early as the 1990s. The lack of pathognomonic elements in corps investigations, where part of the analysis cannot be carried out, requires verification of the value of the investigations that can be carried out, with reference to the biochemical in the present case, in establishing the diagnosis with certainty.

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