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Differential hnRNP D isoform incorporation may confer plasticity to the ESSV-mediated repressive state across HIV-1 exon 3.
Biochim Biophys Acta Gene Regul Mech. 2017 Feb; 1860(2):205-217.BB

Abstract

Even though splicing repression by hnRNP complexes bound to exonic sequences is well-documented, the responsible effector domains of hnRNP proteins have been described for only a select number of hnRNP constituents. Thus, there is only limited information available for possible varying silencer activities amongst different hnRNP proteins and composition changes within possible hnRNP complex assemblies. In this study, we identified the glycine-rich domain (GRD) of hnRNP proteins as a unifying feature in splice site repression. We also show that all four hnRNP D isoforms can act as genuine splicing repressors when bound to exonic positions. The presence of an extended GRD, however, seemed to potentiate the hnRNP D silencer activity of isoforms p42 and p45. Moreover, we demonstrate that hnRNP D proteins associate with the HIV-1 ESSV silencer complex, probably through direct recognition of "UUAG" sequences overlapping with the previously described "UAGG" motifs bound by hnRNP A1. Consequently, this spatial proximity seems to cause mutual interference between hnRNP A1 and hnRNP D. This interplay between hnRNP A1 and D facilitates a dynamic regulation of the repressive state of HIV-1 exon 3 which manifests as fluctuating relative levels of spliced vpr- and unspliced gag/pol-mRNAs.

Authors+Show Affiliations

Institute of Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.Institute of Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.Institute of Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.Institute of Evolutionary Genetics, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany.Institute of Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany.Institute of Virology, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany; Institute for Genetics and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany. Electronic address: steffen.erkelenz@gmx.de.

Pub Type(s)

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

Language

eng

PubMed ID

27919832

Citation

Hillebrand, Frank, et al. "Differential hnRNP D Isoform Incorporation May Confer Plasticity to the ESSV-mediated Repressive State Across HIV-1 Exon 3." Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms, vol. 1860, no. 2, 2017, pp. 205-217.
Hillebrand F, Peter JO, Brillen AL, et al. Differential hnRNP D isoform incorporation may confer plasticity to the ESSV-mediated repressive state across HIV-1 exon 3. Biochim Biophys Acta Gene Regul Mech. 2017;1860(2):205-217.
Hillebrand, F., Peter, J. O., Brillen, A. L., Otte, M., Schaal, H., & Erkelenz, S. (2017). Differential hnRNP D isoform incorporation may confer plasticity to the ESSV-mediated repressive state across HIV-1 exon 3. Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms, 1860(2), 205-217. https://doi.org/10.1016/j.bbagrm.2016.12.001
Hillebrand F, et al. Differential hnRNP D Isoform Incorporation May Confer Plasticity to the ESSV-mediated Repressive State Across HIV-1 Exon 3. Biochim Biophys Acta Gene Regul Mech. 2017;1860(2):205-217. PubMed PMID: 27919832.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential hnRNP D isoform incorporation may confer plasticity to the ESSV-mediated repressive state across HIV-1 exon 3. AU - Hillebrand,Frank, AU - Peter,Jan Otto, AU - Brillen,Anna-Lena, AU - Otte,Marianne, AU - Schaal,Heiner, AU - Erkelenz,Steffen, Y1 - 2016/12/03/ PY - 2016/07/27/received PY - 2016/11/22/revised PY - 2016/12/01/accepted PY - 2016/12/7/pubmed PY - 2017/10/27/medline PY - 2016/12/7/entrez KW - HIV-1 KW - Splicing KW - hnRNP D KW - hnRNP proteins SP - 205 EP - 217 JF - Biochimica et biophysica acta. Gene regulatory mechanisms JO - Biochim Biophys Acta Gene Regul Mech VL - 1860 IS - 2 N2 - Even though splicing repression by hnRNP complexes bound to exonic sequences is well-documented, the responsible effector domains of hnRNP proteins have been described for only a select number of hnRNP constituents. Thus, there is only limited information available for possible varying silencer activities amongst different hnRNP proteins and composition changes within possible hnRNP complex assemblies. In this study, we identified the glycine-rich domain (GRD) of hnRNP proteins as a unifying feature in splice site repression. We also show that all four hnRNP D isoforms can act as genuine splicing repressors when bound to exonic positions. The presence of an extended GRD, however, seemed to potentiate the hnRNP D silencer activity of isoforms p42 and p45. Moreover, we demonstrate that hnRNP D proteins associate with the HIV-1 ESSV silencer complex, probably through direct recognition of "UUAG" sequences overlapping with the previously described "UAGG" motifs bound by hnRNP A1. Consequently, this spatial proximity seems to cause mutual interference between hnRNP A1 and hnRNP D. This interplay between hnRNP A1 and D facilitates a dynamic regulation of the repressive state of HIV-1 exon 3 which manifests as fluctuating relative levels of spliced vpr- and unspliced gag/pol-mRNAs. SN - 1874-9399 UR - https://www.unboundmedicine.com/medline/citation/27919832/Differential_hnRNP_D_isoform_incorporation_may_confer_plasticity_to_the_ESSV_mediated_repressive_state_across_HIV_1_exon_3_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1874-9399(16)30273-5 DB - PRIME DP - Unbound Medicine ER -