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Results for “bicistronic mRNA”

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3 recordsLinked to original sources
PubMed1977

The bicistronic nature of lens alpha-crystallin 14S mRNA.

The A2 and B2 polypeptide chains of calf lens alpha-crystallin are synthesized on a 14S, 1500-nucleotide mRNA and a 10S, 735-nucleotide mRNA, respectively. The 10S mRNA is theoretically compatible with the size of the B2 chain, but the 14S mRNA contains approximately twice the required number of nucleotides necessary for A2 chain synthesis. This fact raises the question of the function of the additional nucleotide sequence in the 14S mRNA. The following observations on 14S mRNA suggest that it may contain an additional cistron. (i) Under a number of denaturing conditions, 14S mRNA continues to retain its initial size characteristics. (ii) In addition to synthesis of the A2 chain, 14S mRNA directs the synthesis of another polypeptide with the same electrophoretic mobility as that of the B2 chain. (iii) Molecular hybridization of the 14S mRNA with the cDNA produced from the 10S mRNA suggests that 2 mol of the cDNA bind to 1 mol of the 14S mRNA. (iv) Examination of the nucleotide sequences of the 10S and 14S mRNAs by two-dimensional maps of RNase A and T1 digests indicates marked similarity. The overall data suggest that the additional cistronic component may carry coding information for an alpha-crystallin polypeptide or a closely related polypeptide species.

Animals↗
PubMed2025

Translation of the downstream ORF from bicistronic mRNAs by human cells: Impact of codon usage and splicing in the upstream ORF.

Biochemistry textbooks describe eukaryotic mRNAs as monocistronic. However, increasing evidence reveals the widespread presence and translation of upstream open reading frames preceding the "main" ORF. DNA and RNA viruses infecting eukaryotes often produce polycistronic mRNAs and viruses have evolved multiple ways of manipulating the host's translation machinery. Here, we introduce an experimental model to study gene expression regulation from virus-like bicistronic mRNAs in human cells. The model consists of a short upstream ORF and a reporter downstream ORF encoding a fluorescent protein. We have engineered synonymous variants of the upstream ORF to explore large parameter space, including codon usage preferences, mRNA folding features, and splicing propensity. We show that human translation machinery can translate the downstream ORF from bicistronic mRNAs, albeit reporter protein levels are thousand times lower than those from the upstream ORF. Furthermore, synonymous recoding of the upstream ORF exclusively during elongation significantly influences its own translation efficiency, reveals cryptic splice signals, and modulates the probability of downstream ORF translation. Our results are consistent with a leaky scanning mechanism facilitating downstream ORF translation from bicistronic mRNAs in human cells, offering new insights into the role of upstream ORFs in translation regulation.

Humans↗
PubMed2025

Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging.

Human hematopoietic stem and progenitor cell (HSPC) fitness declines following exposure to stressors that reduce survival, dormancy, telomere maintenance, and self-renewal, thereby accelerating aging. While previous National Aeronautics and Space Administration (NASA) research revealed immune dysfunction in low-earth orbit (LEO), the impact of spaceflight on human HSPC aging had not been studied. To study HSPC aging, our NASA-supported Integrated Space Stem Cell Orbital Research (ISSCOR) team developed bone marrow niche nanobioreactors with lentiviral bicistronic fluorescent, ubiquitination-based cell-cycle indicator (FUCCI2BL) reporter for real-time HSPC tracking in artificial intelligence (AI)-driven CubeLabs. In month-long International Space Station (ISS) missions (SpX-24, SpX-25, SpX-26, and SpX-27) compared with ground controls, FUCCI2BL reporter, whole-genome and transcriptome sequencing, and cytokine arrays demonstrated cell-cycle, inflammatory cytokine, mitochondrial gene, human repetitive element, and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) deregulation together with clonal hematopoietic mutations. Furthermore, HSPC functionally organized multi-omics aging (HSPC-FOMA) analyses revealed reduced telomere maintenance, adenosine deaminase acting on RNA1 (ADAR1) p150 self-renewal gene expression, and replating capacity indicative of space-associated HSPC aging that may limit long-duration spaceflight.

Humans↗