The Effect of a Single Nucleotide Substitution in the Splicing Silencer in the tat/rev Intron on HIV Type 1 Envelope Expression

Saowakon Paca-Uccaralertkun; Christian Kroun Damgaard; Prasert Auewarakul; Arunee Thitithanyanont; Pirada Suphaphiphat; Max Essex; Jørgen Kjems; Tun-Hou Lee

doi:10.1089/aid.2006.22.76

The Effect of a Single Nucleotide Substitution in the Splicing Silencer in the tat/rev Intron on HIV Type 1 Envelope Expression

Saowakon Paca-Uccaralertkun, Christian Kroun Damgaard, Prasert Auewarakul, Arunee Thitithanyanont, Pirada Suphaphiphat, Max Essex, Jørgen Kjems, Tun-Hou Lee

Department of Molecular Biology and Genetics

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

5 Citations (Scopus)

Abstract

A complex mRNA splicing pattern, which remains to be fully characterized, influences HIV-1 gene expression. In this study, poor envelope expression of a primary HIV-1 isolate was observed and linked to increased splicing of the two coding exons of tat/rev. The substitution of a nucleotide G, located 28 nucleotides upstream of the splice acceptor site SA7 in the recently identified intron splicing silencer sequence, was found to be responsible for the poor envelope expression. A single nucleotide substitution of G with A at this position results in a poor envelope expression phenotype. Moreover, substitution of the nucleotide G with any other nucleotide in an infectious HIV-1 proviral clone, HXB2RU3, results in poor envelope expression. The substitution of this nucleotide reduces the hnRNP A1 binding affinity but increases the splicing of env mRNA. The nucleotide G at this position is highly conserved among HIV-1 isolates and appears to play a critical role in HIV-1 splicing.

Original language	English
Journal	AIDS Research and Human Retroviruses
Volume	22
Issue	1
Pages (from-to)	76-82
Number of pages	7
ISSN	0889-2229
DOIs	https://doi.org/10.1089/aid.2006.22.76
Publication status	Published - 26 Jan 2006

Keywords

Animals
Base Sequence
COS Cells
Cercopithecus aethiops
Gene Expression
Gene Products, rev
Gene Silencing
Genes, tat
HIV-1
Introns
Point Mutation
Protein Binding
RNA Splicing
RNA, Messenger
RNA, Viral
rev Gene Products, Human Immunodeficiency Virus

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title = "The Effect of a Single Nucleotide Substitution in the Splicing Silencer in the tat/rev Intron on HIV Type 1 Envelope Expression",

abstract = "A complex mRNA splicing pattern, which remains to be fully characterized, influences HIV-1 gene expression. In this study, poor envelope expression of a primary HIV-1 isolate was observed and linked to increased splicing of the two coding exons of tat/rev. The substitution of a nucleotide G, located 28 nucleotides upstream of the splice acceptor site SA7 in the recently identified intron splicing silencer sequence, was found to be responsible for the poor envelope expression. A single nucleotide substitution of G with A at this position results in a poor envelope expression phenotype. Moreover, substitution of the nucleotide G with any other nucleotide in an infectious HIV-1 proviral clone, HXB2RU3, results in poor envelope expression. The substitution of this nucleotide reduces the hnRNP A1 binding affinity but increases the splicing of env mRNA. The nucleotide G at this position is highly conserved among HIV-1 isolates and appears to play a critical role in HIV-1 splicing.",

keywords = "Animals, Base Sequence, COS Cells, Cercopithecus aethiops, Gene Expression, Gene Products, rev, Gene Silencing, Genes, tat, HIV-1, Introns, Point Mutation, Protein Binding, RNA Splicing, RNA, Messenger, RNA, Viral, rev Gene Products, Human Immunodeficiency Virus",

author = "Saowakon Paca-Uccaralertkun and Damgaard, {Christian Kroun} and Prasert Auewarakul and Arunee Thitithanyanont and Pirada Suphaphiphat and Max Essex and J{\o}rgen Kjems and Tun-Hou Lee",

year = "2006",

month = jan,

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doi = "10.1089/aid.2006.22.76",

language = "English",

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journal = "AIDS Research and Human Retroviruses",

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The Effect of a Single Nucleotide Substitution in the Splicing Silencer in the tat/rev Intron on HIV Type 1 Envelope Expression. / Paca-Uccaralertkun, Saowakon; Damgaard, Christian Kroun; Auewarakul, Prasert et al.
In: AIDS Research and Human Retroviruses, Vol. 22, No. 1, 26.01.2006, p. 76-82.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The Effect of a Single Nucleotide Substitution in the Splicing Silencer in the tat/rev Intron on HIV Type 1 Envelope Expression

AU - Paca-Uccaralertkun, Saowakon

AU - Damgaard, Christian Kroun

AU - Auewarakul, Prasert

AU - Thitithanyanont, Arunee

AU - Suphaphiphat, Pirada

AU - Essex, Max

AU - Kjems, Jørgen

AU - Lee, Tun-Hou

PY - 2006/1/26

Y1 - 2006/1/26

N2 - A complex mRNA splicing pattern, which remains to be fully characterized, influences HIV-1 gene expression. In this study, poor envelope expression of a primary HIV-1 isolate was observed and linked to increased splicing of the two coding exons of tat/rev. The substitution of a nucleotide G, located 28 nucleotides upstream of the splice acceptor site SA7 in the recently identified intron splicing silencer sequence, was found to be responsible for the poor envelope expression. A single nucleotide substitution of G with A at this position results in a poor envelope expression phenotype. Moreover, substitution of the nucleotide G with any other nucleotide in an infectious HIV-1 proviral clone, HXB2RU3, results in poor envelope expression. The substitution of this nucleotide reduces the hnRNP A1 binding affinity but increases the splicing of env mRNA. The nucleotide G at this position is highly conserved among HIV-1 isolates and appears to play a critical role in HIV-1 splicing.

AB - A complex mRNA splicing pattern, which remains to be fully characterized, influences HIV-1 gene expression. In this study, poor envelope expression of a primary HIV-1 isolate was observed and linked to increased splicing of the two coding exons of tat/rev. The substitution of a nucleotide G, located 28 nucleotides upstream of the splice acceptor site SA7 in the recently identified intron splicing silencer sequence, was found to be responsible for the poor envelope expression. A single nucleotide substitution of G with A at this position results in a poor envelope expression phenotype. Moreover, substitution of the nucleotide G with any other nucleotide in an infectious HIV-1 proviral clone, HXB2RU3, results in poor envelope expression. The substitution of this nucleotide reduces the hnRNP A1 binding affinity but increases the splicing of env mRNA. The nucleotide G at this position is highly conserved among HIV-1 isolates and appears to play a critical role in HIV-1 splicing.

KW - Animals

KW - Base Sequence

KW - COS Cells

KW - Cercopithecus aethiops

KW - Gene Expression

KW - Gene Products, rev

KW - Gene Silencing

KW - Genes, tat

KW - HIV-1

KW - Introns

KW - Point Mutation

KW - Protein Binding

KW - RNA Splicing

KW - RNA, Messenger

KW - RNA, Viral

KW - rev Gene Products, Human Immunodeficiency Virus

U2 - 10.1089/aid.2006.22.76

DO - 10.1089/aid.2006.22.76

M3 - Journal article

C2 - 16438649

SN - 0889-2229

VL - 22

SP - 76

EP - 82

JO - AIDS Research and Human Retroviruses

JF - AIDS Research and Human Retroviruses

IS - 1

ER -

The Effect of a Single Nucleotide Substitution in the Splicing Silencer in the tat/rev Intron on HIV Type 1 Envelope Expression

Abstract

Keywords

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