Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor-II (IGF-II) mRNA exists as multiple transcript size classes, such as 6.0, 5.3, 4.9, 3.2, and 2.2 kb mRNAs in various human tissues. Three different promoters, 2 different polyadenylation sites, and alternative splicing are involved in producing these multiple transcripts. Initiation of transcription at the 3 different promoters results in multiple mRNAs which contain identical coding regions but different 5'-untranslated regions (5'-UTRs). The first promoter is thought to direct expression of 5.3 kb mRNA in adult human liver. The second promoter region directs expression of 6.0, 3.2, and 2.2 kb mRNAs in human fetal tissues and several adult nonliver tissues. The third promoter specifies transcription of a 4.9 kb mRNA in various tissues. We isolated and sequenced a cDNA clone (pIGF-II-1-70) from a human placental cDNA library, which contains the IGF-II coding region and the 5'-UTR associated with the third promoter. By using a 5'-UTR-specific probe from the clone, we found that this third 5'-UTR is contained in the IGF-II mRNA of 2.2 kb and is absent in the 3.2 kb IGF-II mRNA. We also found an 0.9 kb transcript expressed in placenta, which hybridized strongly to the third 5'-UTR specific probe but not to IGF-II coding region probes. This finding might indicate the existence of an mRNA encoding an IGF-II-associated peptide.
Mol Reprod Dev 1992 Dec
PMID:The third IGF-II promoter specifies transcription of three transcripts out of five in human placenta. 128 23

Myxococcus xanthus is a Gram-negative bacterium which has a complex life cycle that includes development (fruiting body formation). The gene for myxobacterial haemagglutinin, mbhA, is developmentally regulated and highly expressed. In this report we show that the mbhA mRNA is exceptionally stable for a prokaryotic organism, exhibiting a chemical half life (t1/2) of 150 min at 18 h of development. The mbhA mRNA was not stable in vegetatively growing cells nor was it stable when expressed in Escherichia coli. We have used site-directed mutagenesis of the mbhA gene to analyse some of the determinants which mediate the stability of the mbhA transcript. Sequences within the 3'-untranslated region (3'-UTR) were found to be crucial for mRNA stability. This region of mRNA can potentially form an extremely stable stem-loop structure immediately adjacent to the translational stop codon. A deletion within this region caused a 10-fold increase in the decay rate of the transcript. Furthermore, conditions which were associated with reduced mbhA translation or mutations that caused premature termination of translation drastically reduced mRNA stability even in the presence of the wild type 3'-UTR. These results suggest that a significant aspect of mbhA mRNA stability involves a synergistic interaction of the translational machinery with sequence elements within the 3'-UTR.
Mol Microbiol 1992 Oct
PMID:Determinants of an unusually stable mRNA in the bacterium Myxococcus xanthus. 147 89

A full length human androgen receptor (hAR) cDNA was constructed from cDNA and genomic clones. Structurally the 10.6-kilobase (kb) hAR cDNA consists of a long 5'-untranslated region (5'-UTR, 1.1 kb), a previously described open reading frame (ORF, 2.7 kb) (Trapman, J., Klaassen, P., Kuiper, G. G. J. M., van der Korput, J. A. G. M., Faber, P. W., van Rooij, H. C. J., Geurts van Kessel, A., Voorhorst, M. M., Mulder, E., and Brinkmann, A. O. (1988) Biochem. Biophys. Res. Commun. 153, 241-248; Faber, P. W., Kuiper, G. G. J. M., van Rooij, H. C. J., van der Korput, J. A. G. M., Brinkmann, A. O., and Trapman, J. (1989) Mol. Cell. Endocrinol. 61, 257-262), and a very long 3'-untranslated region (3'-UTR, 6.8 kb). The complete 5'- and 3'-UTRs were found to be encoded by the previously reported first and eight protein coding exons of the hAR gene, respectively (Kuiper, G. G. J. M., Faber, P. W., van Rooij, H. C. J., van der Korput, J. A. G. M., Ris-Stalpers, C., Klaassen, P., Trapman, J., and Brinkmann, A. O. (1989) J. Mol. Endocrinol. 2, R1-R4). Two major sites of transcription initiation were identified in a 13-base pair region. DNA fragments spanning these transcription initiation sites conferred promoter activity upon a promoterless chloramphenicol acetyltransferase reporter gene construct. Two equally effective, functional polyadenylation signals (ATTAAA and CATAAA) at a mutual distance of 221 base pairs were detected. The ATTAAA hexamer sequence gave rise to multiple sites of poly(A) addition, whereas only one position was used following the CATAAA hexamer. In LNCaP prostatic carcinoma cells an alternatively spliced hAR mRNA species was identified which lacks 3 kb of the 3'-UTR.
 ...
PMID:Characterization of the human androgen receptor transcription unit. 171 Feb 13

Approximately one third of the Na+ channels expressed in denervated or developing skeletal muscle are tetrodotoxin (TTX) insensitive, with a Kd for channel blockade of approximately 1 microM, similar to that found for cardiac Na+ channels. We have recently reported the cloning of a putative Na+ channel subtype that is characteristic of denervated and developing skeletal muscle (SkM2), the deduced amino acid sequence of which is identical to that of a Na+ channel cDNA isolated from heart. We have now examined the functional properties of SkM2 Na+ channels after expression in Xenopus oocytes. We found that the efficiency of expression of constructs containing the SkM2 clone was strongly dependent on the amount of 5'-untranslated region (5'UTR) included. Constructs containing a 206-nucleotide 5'UTR were expressed poorly, whereas constructs from which most of the 5'UTR was removed were expressed well. The channels showed rapid voltage-dependent activation and inactivation. In addition, SkM2 Na+ channels were insensitive to low concentrations of TTX but were ultimately blocked by this toxin, with a Kd of 1.9 microM. The TTX block exhibited use dependence. Finally, SkM2 Na+ channels were not blocked by 100 nM mu-conotoxin, which blocks Na+ channels in innervated skeletal muscle in the low nanomolar concentration range. These data indicate that SkM2 Na+ channels are the TTX-insensitive Na+ channels found in denervated or developing skeletal muscle and are identical to the TTX-insensitive Na+ channels from heart.
Mol Pharmacol 1991 May
PMID:SkM2, a Na+ channel cDNA clone from denervated skeletal muscle, encodes a tetrodotoxin-insensitive Na+ channel. 185 58

The present study examined 1) whether the estrogen-regulated destabilization of albumin mRNA occurs in the nuclear or extranuclear fraction of the liver cell, and 2) whether the selective posttranscriptional regulation of albumin mRNA stability might result from covalent changes introduced in the processing or polyadenylation of the primary transcript. The disappearance of albumin mRNA after estrogen is restricted to the extranuclear fraction of the cell. Transient changes in steady state levels of the mature nuclear transcript were observed that mirrored the transient estrogen-induced changes previously reported for albumin gene transcription. When assayed 24 h after estrogen (when albumin RNA is virtually undetectable in the extranuclear fraction) the steady state levels of both the primary and mature albumin transcripts found in the nucleus were the same as observed in control animals. Estrogen had no effect on the splicing or selection of polyadenylation sites on the 3'-UTR as determined by high resolution gel analysis of the 3'-UTR and DNA sequencing of cDNA clones isolated from a liver library from an estrogen-treated male Xenopus. Most eukaryotic mRNAs have poly(A) tracts several hundred residues in length, and recent studies have demonstrated that a change in the stability of a number of mRNAs correlates directly with the degree of polyadenylation. Albumin contrasts sharply with this, first because it has an exceptionally short poly(A) tail of 17 residues, and second because the degree of polyadenylation is totally unrelated to its destabilization in response to estrogen. These findings indicate that a unique pathway is involved in the regulation of albumin RNA stability by estrogen in Xenopus.
Mol Endocrinol 1989 May
PMID:Extranuclear estrogen-regulated destabilization of Xenopus laevis serum albumin mRNA. 254 54

We have determined the sequences of three recombinant cDNAs complementary to different mouse actin mRNAs that contain more than 90% of the coding sequences and complete or partial 3' untranslated regions (3'UTRs): pAM 91, complementary to the actin mRNA expressed in adult skeletal muscle (alpha sk actin); pAF 81, complementary to an actin mRNA that is accumulated in fetal skeletal muscle and is the major transcript in adult cardiac muscle (alpha c actin); and pAL 41, identified as complementary to a beta nonmuscle actin mRNA on the basis of its 3'UTR sequence. As in other species, the protein sequences of these isoforms are highly (greater than 93%) conserved, but the three mRNAs show significant divergence (13.8-16.5%) at silent nucleotide positions in their coding regions. A nucleotide region located toward the 5' end shows significantly less divergence (5.6-8.7%) among the three mouse actin mRNAs; a second region, near the 3' end, also shows less divergence (6.9%), in this case between the mouse beta and alpha sk actin mRNAs. We propose that recombinational events between actin sequences may have homogenized these regions. Such events distort the calculated evolutionary distances between sequences within a species. Codon usage in the three actin mRNAs is clearly different, and indicates that there is no strict relation between the tissue type, and hence the tRNA precursor pool, and codon usage in these and other muscle mRNAs examined. Analysis of codon usage in these coding sequences in different vertebrate species indicates two tendencies: increases in bias toward the use of G and C in the third codon position in paralogous comparisons (in the order alpha c less than beta less than alpha sk), and in orthologous comparisons (in the order chicken less than rodent less than man). Comparison of actin-coding sequences between species was carried out using the Perler method of analysis. As one moves backward in time, changes at silent sites first accumulate rapidly, then begin to saturate after -(30-40) million years (MY), and actually decrease between -400 and -500 MY. Replacements or silent substitutions therefore cannot be used as evolutionary clocks for these sequences over long periods. Other phenomena, such as gene conversion or isochore compartmentalization, probably distort the estimated divergence time.
J Mol Evol 1986
PMID:Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates. 308 97

The complete 3' untranslated region (3'UTR) sequence of the human skeletal-actin gene has been compared with the corresponding regions of the rat and chicken skeletal-actin genes. This comparison reveals that the skeletal-actin 3'UTR is composed of conserved and nonconserved segments. By using genomic Southern transfer blots and thermal stability (Tm) measurements, we found that the cardiac-actin gene 3'UTR also consists of conserved and nonconserved segments. Comparison of human and Xenopus laevis cardiac-actin mRNA sequences confirms the presence of a region of high similarity in the 3'UTR. We conclude that subsegments of the 3'UTRs of both skeletal- and cardiac-actin genes of birds and mammals are under considerable selective pressure. This suggests that these conserved sequences may have functional roles in actin-gene expression or regulation, and that these roles might be different for each actin isoform.
J Mol Evol 1984
PMID:Evolution of the human sarcomeric-actin genes: evidence for units of selection within the 3' untranslated regions of the mRNAs. 643 77

Two forms of Factor C cDNAs: CrFC21 (3448 bp) and CrFC26 (4182 bp) have been cloned into lambda gt22. CrFC26 includes 568 nucleotides of 5' untranslated region (5' UTR) containing seven ATGs before the real initiation site, an open reading frame (ORF) of 3249 nucleotides, a stop codon, and 365 nucleotides of 3' untranslated sequence. There are four polyadenylation signals and six potential glycosylation sites. The ORF codes for a signal peptide of 24 amino acids and a Factor C zymogen of 1059 residues. The CrFC21 lacks most of the 5' UTR, and has some base changes in its ORF. The predicted secondary mRNA structures of the 5' end of CrFC26 showed numerous stem-and-loop structures, thus obscuring its real start codon. In contrast, CrFC21 has a well-exposed AUG start site, and expresses Factor C in transcription-translation reactions in vitro. There is a typical serine protease catalytic triad of Asp-His-Ser, which is structurally like prothrombin, but catalytically more similar to trypsin. Although an overall homology of 97.7% was observed in comparison with the Tachypleus tridentatus Factor C (TtFC) cDNA, there were notable differences in the restriction sites and subtle base substitutions in the CrFC cDNA. The high degree of homology between Factor C from T. tridentatus and C. rotundicauda substantiates, at the molecular level, the proximity of these two species in the course of evolution. This finding contravenes the apparent disparities with respect to their morphology, ecological habitat, and taxonomical classification.
Mol Mar Biol Biotechnol 1995 Mar
PMID:Molecular cloning and sequence analysis of factor C cDNA from the Singapore horseshoe crab, Carcinoscorpius rotundicauda. 753 1

The Drosophila exuperantia gene (exu) functions in both oogenesis and spermatogenesis. Alternative RNA processing and promoter usage generates sex-specific transcripts which differ in their 5' and 3' untranslated regions, but encode the same predicted protein. We have sequenced the breakpoints of an exu allele which is defective in spermatogenesis but functions normally in oogenesis. This allele deletes most of the sequence specific to the male 3'-UTR, together with some flanking DNA, and causes a reduction in steady-state level of exu mRNA in the testis. In addition, we find that a smaller deletion which removes only sequence within the male 3'-UTR reduces the steady-state level of the mRNA and prevents an exu transgene from rescuing male sterility. Males carrying multiple copies of this transgene are fertile, suggesting that the male-specific 3'-UTR functions to maintain a proper level of exu product in the germline.
Mol Gen Genet 1995 Aug 21
PMID:A male-specific 3'-UTR regulates the steady-state level of the exuperantia mRNA during spermatogenesis in Drosophila. 756 99

Co-suppression of host genes and 35S transgenes encoding nitrate reductase was previously reported in transgenic tobacco plants (Nicotiana tabacum cv. Paraguay or Burley) using either a full-length cDNA or fragments devoid of the 3' and/or 5' UTR. Co-suppression was previously shown to affect a limited fraction of the progeny of one transgenic tobacco line homozygous for a single transgene locus, and the phenomenon occurred at each generation. In this work, 38 combinations of transgene loci derived from 13 independent transgenic lines homozygous for a single transgene locus were field-tested under two different conditions in an attempt to determine the corresponding frequencies of co-suppression, i.e. the percentage of plants showing co-suppression. Each of the 13 homozygous lines exhibited a different frequency of co-suppression, ranging from 0% to 57%. High frequencies were found to be associated with transgene loc carrying a high number of copy of the transgene, suggesting a transgene dose effect. Combinations carrying 2 non-allelic transgene loci in a hemizygous state exhibited frequencies of co-suppression between those of each of the 2 transgene loci in a homozygous state, while combinations carrying 2 non-allelic transgene loci in a homozygous state exhibited frequencies of co-suppression higher than the sum of those of the 2 transgene loci alone in a homozygous state, clearly confirming a transgene dose effect. Co-suppression frequencies were increased when the plants were grown initially in vitro, suggesting some environmental effect. The roles of transgene copy number, number of transgene loci and environmental factors are discussed in the light of a threshold hypothesis.
Plant Mol Biol 1995 Oct
PMID:Field trial analysis of nitrate reductase co-suppression: a comparative study of 38 combinations of transgene loci. 757 60


1 2 3 4 5 6 7 8 9 10 Next >>