title: The 5'UTR in human adenoviruses: leader diversity in late gene expression.
abstract: Human adenoviruses (HAdVs) shut down host cellular cap-dependent mRNA translation while initiating the translation of viral late mRNAs in a cap-independent manner. HAdV 5' untranslated regions (5'UTRs) are crucial for cap-independent initiation, and influence mRNA localization and stability. However, HAdV translational regulation remains relatively uncharacterized. The HAdV tripartite leader (TPL), composed of three introns (TPL 1-3), is critical to the translation of HAdV late mRNA. Herein, we annotated and analyzed 72 HAdV genotypes for the HAdV TPL and another previously described leader, the i-leader. Using HAdV species D, type 37 (HAdV-D37), we show by reverse transcription PCR and Sanger sequencing that mRNAs of the HAdV-D37 E3 transcription unit are spliced to the TPL. We also identified a polycistronic mRNA for RID-α and RID-β. Analysis of the i-leader revealed a potential open reading frame within the leader sequence and the termination of this potential protein in TPL3. A potential new leader embedded within the E3 region was also detected and tentatively named the j-leader. These results suggest an underappreciated complexity of post-transcriptional regulation, and the importance of HAdV 5'UTRs for precisely coordinated viral protein expression along the path from genotype to phenotype.
authors.affiliation: Howe Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, Massachusetts, USA.
authors.forename: Mirja
authors.initials: M
authors.lastname: Ramke
authors.affiliation: Howe Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, Massachusetts, USA.
authors.forename: Jeong Yoon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: David W
authors.identifier: http://orcid.org/0000-0002-6197-1439
authors.initials: DW
authors.lastname: Dyer
authors.affiliation: Bioinformatics and Computational Biology Program, School of Systems Biology, George Mason University, Manassas, Virginia, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Seto
authors.affiliation: Howe Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, Massachusetts, USA. jaya_rajaiya@meei.harvard.edu.
authors.forename: Jaya
authors.initials: J
authors.lastname: Rajaiya
authors.affiliation: Howe Laboratory, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, 243 Charles Street, Boston, Massachusetts, USA. james_chodosh@meei.harvard.edu.
authors.forename: James
authors.initials: J
authors.lastname: Chodosh
mesh_terms: D020121:5' Untranslated Regions; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D015967:Gene Expression Regulation, Viral; D014644:Genetic Variation; D016679:Genome, Viral; D005838:Genotype; D006801:Humans; D009690:Nucleic Acid Conformation; D016366:Open Reading Frames; D010802:Phylogeny; D012333:RNA, Messenger; D012367:RNA, Viral; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; D012367:RNA, Viral