Study of translation control by a RNA helicase A-responsive post-transcriptional control element in Retroviridae
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The Ohio State University / OhioLINK
2008
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=osu1226513076 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-osu12265130762021-08-03T05:54:49Z Study of translation control by a RNA helicase A-responsive post-transcriptional control element in Retroviridae Bolinger, Cheryl Giles Molecular Biology Translation control retrovirus post-transcriptional control element RNA helicase A RHA PCE HIV-1 HTLV-1 IRES:stress granule Mechanisms governing retrovirus translation are a topic of great interest and controversy. Motifs located within the untranslated region (UTR) of retroviral mRNA have established roles in virus replication, and a growing volume of literature is revealing a necessary role of the UTR in control of viral protein synthesis. Two elements implicated in retrovirus translation control are a cap-dependent post-transcriptional control element (PCE) that is responsive to cellular protein RNA helicase A (RHA), or a cap-independent internal ribosome entry site (IRES). We have utilized stringent RNA and protein analyses to show that the 5’ UTR (specifically the RU5 region) of spleen necrosis virus (SNV), reticuloendotheliosis virus A (REV-A), and human T-cell leukemia virus type 1 (HTLV-1) exhibit PCE activity, but not IRES. PCE activity was also conferred by the 5’ UTR of HIV-1 and feline and bovine leukemia viruses, increasing the number of PCE-containing retroviruses to eight viruses spanning 6 genera. SNV, REV-A and HTLV-1 PCE require RHA for activity and it is expected that RHA regulates translation of all PCE-containing mRNA. Direct association of RHA with HTLV-1 and HIV-1 5’ RU5 has been demonstrated, and a combination of ribosomal profile analyses and metabolic labeling experiments determined that RHA is necessary for translation of HTLV-1 and HIV-1 gag from genomic mRNA. These results provide direct evidence that RHA is necessary for efficient HTLV-1 and HIV-1 replication. Targeted RHA mutational analysis identified specific amino acid residues that modulate HTLV-1 PCE activity. The conserved residues that define the redundant N-terminal double-stranded RNA binding domain (dsRBD), the C-terminal arginine-glycine-rich (RGG) bi-directional nuclear transport domain, and central ATPase domain are essential for HTLV-1 translation. Identified transdominant RHA mutants accumulate in cytoplasmic stress granules, presumably with stalled translation complexes. We propose that RHA operates a selective translation control switch of retroviral mRNAs; PCE interaction with RHA through the dsRBD and RGG motif in conjunction with RNP remodeling by the ATPase domain facilitates cap-dependent translation. In the realm of translational research, each new insight into retroviral protein synthesis offers a prospective target for antiviral therapy and strategic improvement of gene transfer vectors. 2008-11-21 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1226513076 http://rave.ohiolink.edu/etdc/view?acc_num=osu1226513076 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
| collection |
NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Molecular Biology Translation control retrovirus post-transcriptional control element RNA helicase A RHA PCE HIV-1 HTLV-1 IRES:stress granule |
| spellingShingle |
Molecular Biology Translation control retrovirus post-transcriptional control element RNA helicase A RHA PCE HIV-1 HTLV-1 IRES:stress granule Bolinger, Cheryl Giles Study of translation control by a RNA helicase A-responsive post-transcriptional control element in Retroviridae |
| author |
Bolinger, Cheryl Giles |
| author_facet |
Bolinger, Cheryl Giles |
| author_sort |
Bolinger, Cheryl Giles |
| title |
Study of translation control by a RNA helicase A-responsive post-transcriptional control element in Retroviridae |
| title_short |
Study of translation control by a RNA helicase A-responsive post-transcriptional control element in Retroviridae |
| title_full |
Study of translation control by a RNA helicase A-responsive post-transcriptional control element in Retroviridae |
| title_fullStr |
Study of translation control by a RNA helicase A-responsive post-transcriptional control element in Retroviridae |
| title_full_unstemmed |
Study of translation control by a RNA helicase A-responsive post-transcriptional control element in Retroviridae |
| title_sort |
study of translation control by a rna helicase a-responsive post-transcriptional control element in retroviridae |
| publisher |
The Ohio State University / OhioLINK |
| publishDate |
2008 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=osu1226513076 |
| work_keys_str_mv |
AT bolingercherylgiles studyoftranslationcontrolbyarnahelicasearesponsiveposttranscriptionalcontrolelementinretroviridae |
| _version_ |
1719427641515180032 |