Expression of the laminin‐A chain is down‐regulated by a non‐canonical polyadenylation signal

Gottschling, Claudia; Huber, Johann; Oberbäumer, Ilse

doi:10.1111/j.1432-1033.1993.tb18144.x

Cited by 10 publications

(5 citation statements)

References 35 publications

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“…Only one possible polyadenylation signal was found. The sequence ATTAAA at position 1769 exhibited homology with a human laminin A noncanonical polyadenylation signal; the position of this signal 60 bp upstream of the poly(A) tail is also consistent with the information obtained for the laminin A gene (13).…”

Section: Resultssupporting

confidence: 82%

Characterization of aflJ , a Gene Required for Conversion of Pathway Intermediates to Aflatoxin

Meyers

OBrian

et al. 1998

Appl Environ Microbiol

144

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The genes encoding the aflatoxin biosynthetic pathway enzymes have been localized as a cluster to a 75-kb DNA fragment. The enzymatic functions of the products of most of the genes in the cluster are known, but there are a few genes that have not yet been characterized. We report here the characterization of one of these genes, a gene designated aflJ. This gene resides in the cluster adjacent to the pathway regulatory gene, aflR, and the two genes are divergently transcribed. Disruption of aflJ inAspergillus flavus results in a failure to produce aflatoxins and a failure to convert exogenously added pathway intermediates norsolorinic acid, sterigmatocystin, andO-methylsterigmatocystin to aflatoxin. The disrupted strain does, however, accumulate pksA, nor-1,ver-1, and omtA transcripts under conditions conducive to aflatoxin biosynthesis. Therefore, disruption ofaflJ does not affect transcription of these genes, andaflJ does not appear to have a regulatory function similar to that of aflR. Sequence analysis of aflJ and its putative peptide, AflJ, did not reveal any enzymatic domains or significant similarities to proteins of known function. The putative peptide does contain three regions predicted to be membrane-spanning domains and a microbodies C-terminal targeting signal.

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Section: Resultssupporting

confidence: 82%

Characterization of aflJ , a Gene Required for Conversion of Pathway Intermediates to Aflatoxin

Meyers

OBrian

et al. 1998

Appl Environ Microbiol

144

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“…The relaxin H2 3 -UTR, however, has a single polyadenylation signal (ATTAAA) that differed from the consensus AATAAA motif. A single base change in relaxin H2 poly (A) + signal may affect its mRNA expression level in a manner similar to the finding by Gottschling et al (1993) that a non-canonical polyadenylation signal (ATTAAA) in the 3 -UTR of laminin-A chain was responsible for the down-regulation of its mRNA and protein expression. Conversely, Sheets et al (1990) reported that, among the rare natural variants of the poly (A) + site, the ATTAAA motif is the most commonly found.…”

Section: Discussionsupporting

confidence: 74%

Isolation and analysis of the 3'-untranslated regions of the human relaxin H1 and H2 genes

Garibay-Tupas

Bao²,

Kim³

et al. 2000

Journal of Molecular Endocrinology

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The human has two relaxins, termed H1 and H2, both of which are biologically active and coexpressed in the decidua, placenta and prostate; in the corpus luteum, the main source of circulating relaxin, only the H2 form is expressed. The reasons for this differential expression of the relaxin genes are unknown. The possibility that their 3 -untranslated regions (UTRs) contribute to this differential expression by affecting their mRNA stabilities was investigated. Thus the 3 -UTRs of both relaxin genes were isolated through a combined 3 -rapid amplification of cDNA ends-PCR (RACE-PCR) using poly (A) + RNA from human decidua, placenta, prostate and corpus luteum. The sequences obtained for each 3 -UTR were identical in the tissues examined, were AT-rich (72%) and showed 91% homology between relaxin H1 and H2 when maximally aligned to include several gaps, the significance of which is unknown. Relaxin H1 has two, and relaxin H2 has one, poly (A) + signal, in addition to one cytoplasmic polyadenylation element 30 nucleotides upstream of this. The mRNA levels of relaxin H1 and H2 in the prostate adenocarcinoma LNCaP.FGC cell line were determined by quantitative competitive RT-PCR. Relaxin H1 had a 10-fold greater number of molecules (2·5 10 7 ) per µg of total RNA than relaxin H2 (2·5 10 6 ). The stability of relaxin H1 and H2 mRNAs were compared in LNCaP cells treated with the transcription inhibitor actinomycin D (10 mM) for 0, 1, 2, 4, 8, 10, 14, or 24 h. Half-lives of 3·17 days for relaxin H1 mRNA and 11·4 h for relaxin H2 mRNA were obtained from semi-logarithmic plots. Thus both mRNAs are relatively stable; however, relaxin H1 mRNA is considerably more stable than relaxin H2, at least in LNCaP cells. This difference in their mRNA stability may partly explain the greater level of expression of relaxin H1 in these cells.

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“…12) In the process of heterotrimer assembly in the endoplasmic reticulum, laminin α chains are considered to be limiting factors. [13][14][15] There are 5 isoforms of laminin α chains and α2, 3, 4, 5 are considered to be expressed in the mouse and human lung (we could not detect the expression of α2 chain immunohistochemically in this study). 16,17) Among them, α3 and α5 chains appear to be derived from epithelial cells.…”

Section: Abstract: Lung -Cancer -Basement Membrane -Lamininmentioning

confidence: 62%

Reduced Expression of Laminin α3 and α5 Chains in Non‐small Cell Lung Cancers

Akashi¹,

Ito²,

Eishi³

et al. 2001

Japanese Journal of Cancer Research

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The basement membrane is considered to act as a barrier which hinders cancer cells from invading the surrounding stroma. In order to assess changes in essential components during neoplasia in the lung, we immunohistochemically studied distribution patterns of laminins α α α α3 and α α α α5 in 40 adenocarcinomas and 8 squamous cell carcinomas. The α α α α5 chain was generally preserved at the periphery, frequently disrupted in foci with alveolar collapse and absent in foci of fibroblastic proliferation within adenocarcinomas. Fragmentation and absence of laminin α α α α3 chain were more prominent than for α α α α5 chain. Laminin α α α α3 chain was partially fragmented or absent in peripheral areas of adenocarcinomas, being significantly different from α α α α5 chain. Non-small cell lung cancers with reduced α α α α5 chain showed a tendency for greater lymph node metastasis. In cultured normal air way epithelial cells, both laminin α α α α3 and α α α α5 chains were found to be expressed by northern analysis. Eleven of the twelve cultured lung cancer cell lines did not express α α α α3 chain and expression of α α α α5 chain was reduced in three. Quantitative RT-PCR analysis also demonstrated expression of laminin α α α α3 chain in adenocarcinoma tissues to be significantly lower than in normal lung tissues.These results suggest that expression of laminin α α α α chains is often reduced in lung cancer cells and this might contribute to basement membrane fragmentation and subsequent proliferation of stromal elements, as well as play some role in the process of cancer cell invasion.Key words: Lung -Cancer -Basement membrane -LamininIn neoplastic tissue, the basement membrane is considered to act as a barrier which hinders the cancer cells from invading the surrounding stroma.1) With adenocarcinomas of the lung, disruption of basement membrane and linkage with lymph node metastasis and a poor prognosis have been reported. [2][3][4][5] Because the epithelial basement membrane is known to be renewed through turnover over several weeks, 6) two putative processes leading to fragmentation can be hypothesized. One is increased degradation of basement membrane by proteinases, such as collagenase, secreted by the cancer cells themselves or by the surrounding stromal cells. 3,7,8) The other possibility is that a reduced capacity of cancer cells to synthesize basement membrane components might exert an influence.The epithelial basement membrane is considered to be formed from materials secreted by both epithelial and stromal cells.9-11) Laminins, one of the major components of the basement membrane, are heterotrimeric glycoproteins composed of one large α chain and two smaller β and γ chains.12) In the process of heterotrimer assembly in the endoplasmic reticulum, laminin α chains are considered to be limiting factors. [13][14][15] There are 5 isoforms of laminin α chains and α2, 3, 4, 5 are considered to be expressed in the mouse and human lung (we could not detect the expression of α2 chain immunohistochemically in this study)...

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Expression of the laminin‐A chain is down‐regulated by a non‐canonical polyadenylation signal

Cited by 10 publications

References 35 publications

Characterization of aflJ , a Gene Required for Conversion of Pathway Intermediates to Aflatoxin

Characterization of aflJ , a Gene Required for Conversion of Pathway Intermediates to Aflatoxin

Isolation and analysis of the 3'-untranslated regions of the human relaxin H1 and H2 genes

Reduced Expression of Laminin α3 and α5 Chains in Non‐small Cell Lung Cancers

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