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A second exon splicing silencer within human immunodeficiency virus type 1 tat exon 2 represses splicing of Tat mRNA and binds protein hnRNP H.
J Biol Chem. 2001 Nov 02; 276(44):40464-75.JB

Abstract

An equilibrium between spliced and unspliced primary transcripts is essential for retrovirus multiplication. This equilibrium is maintained by the presence of inefficient splice sites. The A3 3'-splice site of human immunodeficiency virus type I (HIV-1) is required for Tat mRNA production. The infrequent utilization of this splice site has been attributed to the presence of a suboptimal polypyrimidine tract and an exonic splicing silencer (ESS2) in tat exon 2 approximately 60 nucleotides downstream of 3'-splice site A3. Here, using site-directed mutagenesis followed by analysis of splicing in vitro and in HeLa cells, we show that the 5' extremity of tat exon 2 contains a second exonic splicing silencer (ESS2p), which acts to repress splice site A3. The inhibitory property of this exonic silencer was active when inserted downstream of another HIV-1 3'-splice site (A2). Protein hnRNP H binds to this inhibitory element, and two U-to-C substitutions within the ESS2p element cause a decreased hnRNP H affinity with a concomitant increase in splicing efficiency at 3'-splice site A3. This suggests that hnRNP H is directly involved in splicing inhibition. We propose that hnRNP H binds to the HIV-1 ESS2p element and competes with U2AF(35) for binding to the exon sequence flanking 3'-splice site A3. This binding results in the inhibition of splicing at 3'-splice site A3.

Authors+Show Affiliations

Laboratoire de Maturation des Acide Ribo-Nucléotidique et Enzymologie Moléculaire, Unité Mixte de Recherche 7567 Université Henri Poincarré-CNRS, Boulevard des Aiguillettes, BP239, 54506 Vandoeuvre-lès-Nancy cedex, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11526107

Citation

Jacquenet, S, et al. "A Second Exon Splicing Silencer Within Human Immunodeficiency Virus Type 1 Tat Exon 2 Represses Splicing of Tat mRNA and Binds Protein hnRNP H." The Journal of Biological Chemistry, vol. 276, no. 44, 2001, pp. 40464-75.
Jacquenet S, Méreau A, Bilodeau PS, et al. A second exon splicing silencer within human immunodeficiency virus type 1 tat exon 2 represses splicing of Tat mRNA and binds protein hnRNP H. J Biol Chem. 2001;276(44):40464-75.
Jacquenet, S., Méreau, A., Bilodeau, P. S., Damier, L., Stoltzfus, C. M., & Branlant, C. (2001). A second exon splicing silencer within human immunodeficiency virus type 1 tat exon 2 represses splicing of Tat mRNA and binds protein hnRNP H. The Journal of Biological Chemistry, 276(44), 40464-75.
Jacquenet S, et al. A Second Exon Splicing Silencer Within Human Immunodeficiency Virus Type 1 Tat Exon 2 Represses Splicing of Tat mRNA and Binds Protein hnRNP H. J Biol Chem. 2001 Nov 2;276(44):40464-75. PubMed PMID: 11526107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A second exon splicing silencer within human immunodeficiency virus type 1 tat exon 2 represses splicing of Tat mRNA and binds protein hnRNP H. AU - Jacquenet,S, AU - Méreau,A, AU - Bilodeau,P S, AU - Damier,L, AU - Stoltzfus,C M, AU - Branlant,C, Y1 - 2001/08/28/ PY - 2001/8/30/pubmed PY - 2002/1/5/medline PY - 2001/8/30/entrez SP - 40464 EP - 75 JF - The Journal of biological chemistry JO - J Biol Chem VL - 276 IS - 44 N2 - An equilibrium between spliced and unspliced primary transcripts is essential for retrovirus multiplication. This equilibrium is maintained by the presence of inefficient splice sites. The A3 3'-splice site of human immunodeficiency virus type I (HIV-1) is required for Tat mRNA production. The infrequent utilization of this splice site has been attributed to the presence of a suboptimal polypyrimidine tract and an exonic splicing silencer (ESS2) in tat exon 2 approximately 60 nucleotides downstream of 3'-splice site A3. Here, using site-directed mutagenesis followed by analysis of splicing in vitro and in HeLa cells, we show that the 5' extremity of tat exon 2 contains a second exonic splicing silencer (ESS2p), which acts to repress splice site A3. The inhibitory property of this exonic silencer was active when inserted downstream of another HIV-1 3'-splice site (A2). Protein hnRNP H binds to this inhibitory element, and two U-to-C substitutions within the ESS2p element cause a decreased hnRNP H affinity with a concomitant increase in splicing efficiency at 3'-splice site A3. This suggests that hnRNP H is directly involved in splicing inhibition. We propose that hnRNP H binds to the HIV-1 ESS2p element and competes with U2AF(35) for binding to the exon sequence flanking 3'-splice site A3. This binding results in the inhibition of splicing at 3'-splice site A3. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/11526107/A_second_exon_splicing_silencer_within_human_immunodeficiency_virus_type_1_tat_exon_2_represses_splicing_of_Tat_mRNA_and_binds_protein_hnRNP_H_ DB - PRIME DP - Unbound Medicine ER -