The sequences and structures of 3'-untranslated regions (3'UTRs) of messenger RNAs govern their stability, localization, and expression. 3'UTR regulatory elements are recognized by a wide variety of -acting factors that include microRNAs (miRNAs), their associated machinery, and RNA-binding proteins (RBPs). In turn, these factors instigate common mechanistic strategies to execute the regulatory programs encoded by 3'UTRs. Here, we review classes of factors that recognize 3'UTR regulatory elements and the effector machineries they guide toward mRNAs to dictate their expression and fate. We outline illustrative examples of competitive, cooperative, and coordinated interplay such as mRNA localization and localized translation. We further review the recent advances in the study of mRNP granules and phase transition, and their possible significance for the functions of 3'UTRs. Finally, we highlight some of the most recent strategies aimed at deciphering the complexity of the regulatory codes of 3'UTRs, and identify some of the important remaining challenges.
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http://dx.doi.org/10.3389/fgene.2019.00006 | DOI Listing |
Elife
January 2025
Innovative Genomics Institute, University of California, Berkeley, Berkeley, United States.
Stem cell differentiation involves a global increase in protein synthesis to meet the demands of specialized cell types. However, the molecular mechanisms underlying this translational burst and the involvement of initiation factors remains largely unknown. Here, we investigate the role of eukaryotic initiation factor 3 (eIF3) in early differentiation of human pluripotent stem cell (hPSC)-derived neural progenitor cells (NPCs).
View Article and Find Full Text PDFTransl Oncol
January 2025
Department of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan 750004, China. Electronic address:
We explored the influence of the TCL6/miR-876-5p axis on breast cancer cell proliferation and migration. Using The Cancer Genome Atlas (TCGA) database, we evaluated the expression of TCL6 in breast cancer patients and studied its effects on cell proliferation, migration, and the cell cycle in vitro. The regulatory effect of miR-876-5p on myosin light chain-2 (MYL2) 3' untranslated regions (3'UTR) was analyzed through luciferase reporter assays, and rescue experiments confirmed TCL6-driven upregulation of MYL2 via a competitive RNA binding mechanism.
View Article and Find Full Text PDFHLA
February 2025
Temple University Hospital Philadelphia, Philadelphia, Pennsylvania, USA.
The full-length sequence of HLA-DQB1*06:304N covers the 5'-untranslated region (UTR), all introns and exons, and the 3' UTR.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
March 2025
Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA.
Lipid nanoparticles (LNPs) are often liver tropic, presenting challenges for LNP-delivered mRNA therapeutics intended for other tissues, as off-target expression in the liver may increase side effects and modulate immune responses. To avoid off-target expression in the liver, miR-122 binding sites have been used by others in viral and non-viral therapeutics. Here, we use a luciferase reporter system to compare different copy numbers and insertion locations of miR-122 binding sequences to restrict liver expression.
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