دورية أكاديمية
SERPINA1 long transcripts produce non-secretory alpha1-antitrypsin isoform: In vitro translation in living cells.
| العنوان: | SERPINA1 long transcripts produce non-secretory alpha1-antitrypsin isoform: In vitro translation in living cells. |
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| المؤلفون: | Maslakova AA; Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119991, Russia. Electronic address: aitsana.dokrunova@gmail.com., Golyshev SA; A.N. Belozersky Institute of Physical and Chemical Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119992, Russia., Potashnikova DM; Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119991, Russia., Moisenovich AM; Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119991, Russia., Orlovsky IV; Research Institute of Molecular and Cellular Medicine, Рeoples' Friendship University of Russia (RUDN University), Miklukho-Maklaya, Moscow 117198, Russia., Smirnova OV; Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119991, Russia., Rubtsov MA; Faculty of Biology, M.V. Lomonosov Moscow State University, Leninskie Gory, Moscow 119991, Russia; Center for Industrial Technologies and Entrepreneurship, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya, Moscow 119991, Russia. |
| المصدر: | International journal of biological macromolecules [Int J Biol Macromol] 2023 Jun 30; Vol. 241, pp. 124433. Date of Electronic Publication: 2023 Apr 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7909578 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0003 (Electronic) Linking ISSN: 01418130 NLM ISO Abbreviation: Int J Biol Macromol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Guildford, Eng., IPC Science and Technology Press. |
| مواضيع طبية MeSH: | alpha 1-Antitrypsin Deficiency*/genetics, Male ; Humans ; Codon, Initiator/genetics ; Alleles ; Protein Isoforms/genetics ; alpha 1-Antitrypsin/genetics |
| مستخلص: | SERPINA1 is a well-studied serpin gene due to its dramatic impact on human health. Translation initiation at the main SERPINA1 start codon produces the only known alpha1-antitrypsin (AAT) isoform intended for secretion. AAT performs essential functions by inhibiting proteases and modulating immunity. However, SERPINA1 expression at the level of translation is not sufficiently studied. Here we hypothesize that the main SERPINA1 ORF can be alternatively translated, producing a non-secretory AAT isoform by either masking or excluding a signal peptide. We defined SERPINA1 long mRNA isoforms specific for prostate (DU145) and liver (HepG2) cell lines and studied their individual expression by in vitro assay. We found that all long transcripts produce both glycosylated secretory AAT-eGFP fusion protein and non-glycosylated intracellular AAT-eGFP (initiated from an alternative AUG-2 start codon), with the proportion regulated by the SERPINA1 5'-UTR. Both fusion proteins localize to distinct cellular compartments: in contrast to a fusion with the secretory AAT accumulating in the ER, the intracellular one exhibits nuclear-cytoplasmic shuttling. We detected putative endogenous AAT isoform enriching the nuclear speckles. CONCLUSION: Alternative translation initiation might be a mechanism through which SERPINA1 expands the biological diversity of its protein products. Our findings open up new prospects for the study of SERPINA1 gene expression. Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2023 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Alpha1-antitrypsin; Non-secretory alpha1-antitrypsin isoform; SERPINA1 long transcript; alpha1-antitrypsin-eGFP fusion protein; altORF; uORF |
| المشرفين على المادة: | 0 (Codon, Initiator) 0 (Protein Isoforms) 0 (SERPINA1 protein, human) 0 (alpha 1-Antitrypsin) |
| تواريخ الأحداث: | Date Created: 20230422 Date Completed: 20230612 Latest Revision: 20230612 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.ijbiomac.2023.124433 |
| PMID: | 37086761 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0003 |
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| DOI: | 10.1016/j.ijbiomac.2023.124433 |