98%
921
2 minutes
20
Several classes of small noncoding RNAs are key players in cellular metabolism including mRNA decoding, RNA processing, and mRNA stability. Here we show that a tRNA(Asp) isodecoder, corresponding to a human tRNA-derived sequence, binds to an embedded Alu RNA element contained in the 3' UTR of the human aspartyl-tRNA synthetase mRNA. This interaction between two well-known classes of RNA molecules, tRNA and Alu RNA, is driven by an unexpected structural motif and induces a global rearrangement of the 3' UTR. Besides, this 3' UTR contains two functional polyadenylation signals. We propose a model where the tRNA/Alu interaction would modulate the accessibility of the two alternative polyadenylation sites and regulate the stability of the mRNA. This unique regulation mechanism would link gene expression to RNA polymerase III transcription and may have implications in a primate-specific signal pathway.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189049 | PMC |
http://dx.doi.org/10.1073/pnas.1103698108 | DOI Listing |
ACS Appl Mater Interfaces
August 2025
Department of Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, Tennessee 37235, United States.
Vaccine adjuvants stimulate innate immunity to enhance and shape adaptive immune responses. However, approved adjuvants typically elicit weak CD8 T cell responses to protein- and peptide-based vaccines, motivating an investigation into the discovery and testing of new adjuvants. Unedited forms of endogenous Alu RNAs are sensed by pattern recognition receptors (PRRs) to trigger sterile inflammation, and therefore we hypothesized that synthetic Alu RNA molecules could be harnessed as vaccine adjuvants.
View Article and Find Full Text PDFFASEB J
August 2025
Department of Ophthalmology, Novartis Biomedical Research, Cambridge, Massachusetts, USA.
RIG-I signaling has been previously implicated as a driver of inflammation to the retinal pigment epithelium (RPE) during age-related macular degeneration (AMD). Double-stranded RNA (dsRNA) is known to initiate RIG-I signaling and lead to a type I interferon response. We show through shRNA knockdown that RIG-I is essential for initiating an interferon response in iPS-RPE in response to both synthetic dsRNA-mimetic 3p-hpRNA and the double-stranded retrotransposable element Alu.
View Article and Find Full Text PDFChin Med J (Engl)
August 2025
State Key Laboratory of Green Biomanufacturing, Tsinghua-Peking Joint Center for Life Sciences, Center for Synthetic and Systems Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Transposable elements (TEs), once considered genomic "junk", are now recognized as critical regulators of genome function and human disease. These mobile genetic elements-including retrotransposons (long interspersed nuclear elements [LINE-1], Alu, short interspersed nuclear element-variable numbers of tandem repeats-Alu [SVA], and human endogenous retrovirus [HERV]) and DNA transposons-are tightly regulated by multilayered mechanisms that operate from transcription through to genomic integration. Although typically silenced in somatic cells, TEs are transiently activated during key developmental stages-such as zygotic genome activation and cell fate determination-where they influence chromatin architecture, transcriptional networks, RNA processing, and innate immune responses.
View Article and Find Full Text PDFCell
July 2025
State Key Laboratory of Green Biomanufacturing, Tsinghua-Peking Joint Center for Life Sciences, Center for Synthetic and Systems Biology, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua University, Beijing, China. Electronic address:
Discrete genomic units can recombine into composite transposons that transcribe and transpose as single units, but their regulation and function are not fully understood. We report that composite transposons harbor bivalent histone marks, with activating and repressive marks in distinct regions. Genome-wide CRISPR-Cas9 screening, using a reporter driven by the hominid-specific composite transposon SVA (SINE [short interspersed nuclear element]-VNTR [variable number of tandem repeats]-Alu) in human cells, identified diverse genes that modify bivalent histone marks to regulate SVA transcription.
View Article and Find Full Text PDFSmall noncoding RNAs perform integral roles in eukaryotic lifecycles, particularly the 7SK snRNA, which is responsible for RNA Polymerase II transcription modulation and progression when interacting with P-TEFb, and the 7SL RNA involved in Signal Recognition Particle mediation of co-translational activities of endoplasmic reticulum-bound proteins. These RNAs retain important secondary structures that interact with proteins involved in regulating transcription and translation. RNA-protein interactions involving the RNA stem-loops have been previously characterised using chemical probing techniques, Cryo-Electron Microscopy, and Nuclear Magnetic Resonance.
View Article and Find Full Text PDF