Mosaic translation hypothesis: chimeric polypeptides produced via multiple ribosomal frameshifting as a basis for adaptability. (17th November 2021)

• Record Type: Journal Article
• Authors: Çakır, Umut; Gabed, Noujoud; Brunet, Marie; Roucou, Xavier; Kryvoruchko, Igor
• Is Part Of: FEBS journal. Volume 290:Number 2(2023)
• Page Start: 370
• Page End: 378
• Publication Date: 2021-11-17
• Subjects: alternative open reading frame -- chimeric protein -- mass spectrometry -- protein coding potential -- ribosomal frameshifting -- translation; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 572
• DOI: 10.1111/febs.16269
• Languages: English
• ISSNs: 1742-464X

Abstract

Abstract : How many different proteins can be produced from a single spliced transcript? Genome annotation projects overlook the coding potential of reading frames other than that of the reference open reading frames (refORFs). Recently, alternative open reading frames (altORFs) and their translational products, alternative proteins, have been shown to carry out important functions in various organisms. AltORFs overlapping refORFs or other altORFs in a different reading frame may be involved in one fundamental mechanism so far overlooked. A few years ago, it was proposed that altORFs may act as building blocks for chimeric (mosaic) polypeptides, which are produced via multiple ribosomal frameshifting events from a single mature transcript. We adopt terminology from that earlier discussion and call this mechanism mosaic translation. This way of extracting and combining genetic information may significantly increase proteome diversity. Thus, we hypothesize that this mechanism may have contributed to the flexibility and adaptability of organisms to a variety of environmental conditions. Specialized ribosomes acting as sensors probably played a central role in this process. Importantly, mosaic translation may be the main source of protein diversity in genomes that lack alternative splicing. The idea of mosaic translation is a testable hypothesis, although its direct demonstration is challenging. Should mosaic translation occur, we would currently highly underestimate the complexity of translation mechanisms and thus the proteome. Abstract : Under the hypothesis of mosaic translation, multiple ribosomal frameshifting events result in the translation of genetic information present in all three reading frames of mature transcripts. Mosaic translation would thus yield chimeric (mosaic) proteins currently absent from common biorepositories. If confirmed, this mechanism could considerably heighten the diversity and complexity of proteomes. Hence, mosaic translation may provide many biological advantages to organisms, including more substantial adaptive potential.