A novel calcitonin carboxyl-terminal peptide produced in medullary thyroid carcinoma by alternative RNA processing of the calcitonin/calcitonin gene-related peptide gene

The calcitonin/calcitonin gene-related peptide gene expresses two different mRNAs by tissue-specific alternative processing. The calcitonin mRNA is produced in thyroid C cells by splicing of the first three exons to the fourth polyadenylated exon. It encodes a protein precursor containing an amino-t...

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Veröffentlicht in:The Journal of biological chemistry 1991-12, Vol.266 (36), p.24627-24631
Hauptverfasser: MINVIELLE, S, GISCARD-DARTEVELLE, S, COHEN, R, TABOULET, J, LABYE, F, JULIENNE, A, RIVAILLE, P, MILHAUD, G, MOUKHTAR, M. S.K, LASMOLES, F
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container_end_page 24631
container_issue 36
container_start_page 24627
container_title The Journal of biological chemistry
container_volume 266
creator MINVIELLE, S
GISCARD-DARTEVELLE, S
COHEN, R
TABOULET, J
LABYE, F
JULIENNE, A
RIVAILLE, P
MILHAUD, G
MOUKHTAR, M. S.K
LASMOLES, F
description The calcitonin/calcitonin gene-related peptide gene expresses two different mRNAs by tissue-specific alternative processing. The calcitonin mRNA is produced in thyroid C cells by splicing of the first three exons to the fourth polyadenylated exon. It encodes a protein precursor containing an amino-terminal peptide, calcitonin, and a carboxyl-terminal peptide (CCP I). Calcitonin gene-related peptide (CGRP) mRNA is produced in neuronal cells by splicing of the three common exons to the fifth exon and the polyadenylated sixth exon, leading to the production of a CGRP precursor. Our studies concerning the expression of the calcitonin/CGRP gene in human medullary thyroid carcinoma revealed the presence of a new RNA transcript. Amplification by polymerase chain reaction and direct sequencing showed that the novel transcript is composed of exons 1, 2, and 3, part of exon 4, exon 5, and a polyadenylated exon 6. This transcript contains an open reading frame coding for the known amino-terminal and calcitonin peptides, as well as for a novel calcitonin carboxyl-terminal peptide, CCP II. This third alternative pathway utilizes an internal donor site within the exon coding for calcitonin. The presence of CCP II was demonstrated in plasma and thyroidal tissues of medullary thyroid carcinoma patients, implying that this novel mRNA is actively translated in medullary thyroid carcinoma.
doi_str_mv 10.1016/S0021-9258(18)54275-7
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S.K</creatorcontrib><creatorcontrib>LASMOLES, F</creatorcontrib><title>A novel calcitonin carboxyl-terminal peptide produced in medullary thyroid carcinoma by alternative RNA processing of the calcitonin/calcitonin gene-related peptide gene</title><title>The Journal of biological chemistry</title><addtitle>J Biol Chem</addtitle><description>The calcitonin/calcitonin gene-related peptide gene expresses two different mRNAs by tissue-specific alternative processing. The calcitonin mRNA is produced in thyroid C cells by splicing of the first three exons to the fourth polyadenylated exon. It encodes a protein precursor containing an amino-terminal peptide, calcitonin, and a carboxyl-terminal peptide (CCP I). Calcitonin gene-related peptide (CGRP) mRNA is produced in neuronal cells by splicing of the three common exons to the fifth exon and the polyadenylated sixth exon, leading to the production of a CGRP precursor. Our studies concerning the expression of the calcitonin/CGRP gene in human medullary thyroid carcinoma revealed the presence of a new RNA transcript. Amplification by polymerase chain reaction and direct sequencing showed that the novel transcript is composed of exons 1, 2, and 3, part of exon 4, exon 5, and a polyadenylated exon 6. This transcript contains an open reading frame coding for the known amino-terminal and calcitonin peptides, as well as for a novel calcitonin carboxyl-terminal peptide, CCP II. This third alternative pathway utilizes an internal donor site within the exon coding for calcitonin. The presence of CCP II was demonstrated in plasma and thyroidal tissues of medullary thyroid carcinoma patients, implying that this novel mRNA is actively translated in medullary thyroid carcinoma.</description><subject>Amino Acid Sequence</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Blotting, Northern</subject><subject>Calcitonin - biosynthesis</subject><subject>Calcitonin - blood</subject><subject>Calcitonin - metabolism</subject><subject>calcitonin gene-related peptide</subject><subject>Calcitonin Gene-Related Peptide - genetics</subject><subject>Chromatography, Affinity</subject><subject>DNA, Neoplasm</subject><subject>Exons</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>genes</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>Molecular and cellular biology</subject><subject>Molecular genetics</subject><subject>Molecular Sequence Data</subject><subject>Peptide Fragments - biosynthesis</subject><subject>Peptide Fragments - blood</subject><subject>Peptide Fragments - metabolism</subject><subject>Polymerase Chain Reaction</subject><subject>Protein Biosynthesis</subject><subject>RNA</subject><subject>RNA Splicing</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Neoplasm - metabolism</subject><subject>Thyroid Neoplasms - genetics</subject><subject>Thyroid Neoplasms - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transcription. Transcription factor. Splicing. 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Psychology</topic><topic>genes</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>Molecular and cellular biology</topic><topic>Molecular genetics</topic><topic>Molecular Sequence Data</topic><topic>Peptide Fragments - biosynthesis</topic><topic>Peptide Fragments - blood</topic><topic>Peptide Fragments - metabolism</topic><topic>Polymerase Chain Reaction</topic><topic>Protein Biosynthesis</topic><topic>RNA</topic><topic>RNA Splicing</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Neoplasm - metabolism</topic><topic>Thyroid Neoplasms - genetics</topic><topic>Thyroid Neoplasms - metabolism</topic><topic>Transcription, Genetic</topic><topic>Transcription. Transcription factor. Splicing. 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S.K</au><au>LASMOLES, F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel calcitonin carboxyl-terminal peptide produced in medullary thyroid carcinoma by alternative RNA processing of the calcitonin/calcitonin gene-related peptide gene</atitle><jtitle>The Journal of biological chemistry</jtitle><addtitle>J Biol Chem</addtitle><date>1991-12-25</date><risdate>1991</risdate><volume>266</volume><issue>36</issue><spage>24627</spage><epage>24631</epage><pages>24627-24631</pages><issn>0021-9258</issn><eissn>1083-351X</eissn><coden>JBCHA3</coden><abstract>The calcitonin/calcitonin gene-related peptide gene expresses two different mRNAs by tissue-specific alternative processing. The calcitonin mRNA is produced in thyroid C cells by splicing of the first three exons to the fourth polyadenylated exon. It encodes a protein precursor containing an amino-terminal peptide, calcitonin, and a carboxyl-terminal peptide (CCP I). Calcitonin gene-related peptide (CGRP) mRNA is produced in neuronal cells by splicing of the three common exons to the fifth exon and the polyadenylated sixth exon, leading to the production of a CGRP precursor. Our studies concerning the expression of the calcitonin/CGRP gene in human medullary thyroid carcinoma revealed the presence of a new RNA transcript. Amplification by polymerase chain reaction and direct sequencing showed that the novel transcript is composed of exons 1, 2, and 3, part of exon 4, exon 5, and a polyadenylated exon 6. This transcript contains an open reading frame coding for the known amino-terminal and calcitonin peptides, as well as for a novel calcitonin carboxyl-terminal peptide, CCP II. This third alternative pathway utilizes an internal donor site within the exon coding for calcitonin. The presence of CCP II was demonstrated in plasma and thyroidal tissues of medullary thyroid carcinoma patients, implying that this novel mRNA is actively translated in medullary thyroid carcinoma.</abstract><cop>Bethesda, MD</cop><pub>American Society for Biochemistry and Molecular Biology</pub><pmid>1761559</pmid><doi>10.1016/S0021-9258(18)54275-7</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record>
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ispartof The Journal of biological chemistry, 1991-12, Vol.266 (36), p.24627-24631
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subjects Amino Acid Sequence
Base Sequence
Biological and medical sciences
Blotting, Northern
Calcitonin - biosynthesis
Calcitonin - blood
Calcitonin - metabolism
calcitonin gene-related peptide
Calcitonin Gene-Related Peptide - genetics
Chromatography, Affinity
DNA, Neoplasm
Exons
Fundamental and applied biological sciences. Psychology
genes
Humans
Immunohistochemistry
Molecular and cellular biology
Molecular genetics
Molecular Sequence Data
Peptide Fragments - biosynthesis
Peptide Fragments - blood
Peptide Fragments - metabolism
Polymerase Chain Reaction
Protein Biosynthesis
RNA
RNA Splicing
RNA, Messenger - metabolism
RNA, Neoplasm - metabolism
Thyroid Neoplasms - genetics
Thyroid Neoplasms - metabolism
Transcription, Genetic
Transcription. Transcription factor. Splicing. Rna processing
title A novel calcitonin carboxyl-terminal peptide produced in medullary thyroid carcinoma by alternative RNA processing of the calcitonin/calcitonin gene-related peptide gene
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