title: Translational Initiation at a Non-AUG Start Codon for Human and Mouse Negative Elongation Factor-B.
abstract: Negative elongation factor (NELF), a four-subunit protein complex in metazoan, plays an important role in regulating promoter-proximal pausing of RNA polymerase II (RNAPII). Genetic studies demonstrate that the B subunit of mouse NELF (NELF-B) is critical for embryonic development and homeostasis in adult tissue. We report here that both human and mouse NELF-B proteins are translated from a non-AUG codon upstream of the annotated AUG. This non-AUG codon sequence is conserved in mammalian NELF-B but not NELF-B orthologs of lower metazoan. The full-length and a truncated NELF-B that starts at the first AUG codon both interact with the other three NELF subunits. Furthermore, these two forms of NELF-B have a similar impact on the transcriptomics and proliferation of mouse embryonic fibroblasts. These results strongly suggest that additional amino acid sequence upstream of the annotated AUG is dispensable for the essential NELF function in supporting cell growth in vitro. The majority of mouse adult tissues surveyed express the full-length NELF-B protein, and some contain a truncated NELF-B protein with the same apparent size as the AUG-initiated version. This result raises the distinct possibility that translational initiation of mouse NELF-B is regulated in a tissue-dependent manner.
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, United States of America.
authors.forename: Haihui
authors.initials: H
authors.lastname: Pan
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, United States of America.
authors.forename: Xiayan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, United States of America.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo, 11835, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abouelsoud
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, United States of America.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Illumina, Inc., San Diego, CA, 92121, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: April
authors.affiliation: Department of Biology, School of Sciences and Engineering, The American University in Cairo, New Cairo, 11835, Egypt.
authors.forename: Asma
authors.initials: A
authors.lastname: Amleh
authors.affiliation: Illumina, Inc., San Diego, CA, 92121, United States of America.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, United States of America.
authors.forename: Yanfen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Molecular Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, United States of America.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation; D018387:Codon, Initiator / Q000235:genetics*; D017124:Conserved Sequence / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology; D005091:Exons / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008322:Mammals / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010442:Peptide Chain Initiation, Translational / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D018387:Codon, Initiator; D014157:Transcription Factors; C118437:negative elongation factor