bims-micpro 2025-07-06 papers

Sci Rep. 2025 Jul 02. 15(1): 22800

Alternative splicing in the RBMXL1 5'-UTR induces uORF-mediated translation control in activated B lymphocytes.

Sylvain de Breyne, Hélène Polvèche, Didier Auboeuf, Théophile Ohlmann, Henri Gruffat, Evelyne Manet.

The RNA binding motif X-linked (RBMX) gene plays multiple roles in gene transcription and alternative splicing regulation. Modifications to its expression have been associated with the development of various cancers. In addition to RBMX, there exist several RBMX-like genes (RBMXLs) that have been generated by retrotransposition of RBMX. Among these, RBMXL1 encodes a protein that is more than 95% identical to RBMX and may therefore fulfil similar functions. This study identified a specific variation in the alternative splicing of a small exon located in the 5'-untranslated region of the human RBMXL1 mRNA. This occurs following the infection of primary B lymphocytes by the Epstein-Barr virus (EBV) or their activation by a combination of CD40 Ligand and Interleukin 4. The inclusion of this small exon creates a small upstream open reading frame (uORF). Such uORFs have been described as having the capacity to regulate the translation of a downstream ORF. Our findings indicate that the RBMXL1 uORF is functional and that its presence results in the downregulation of the translation of the downstream primary ORF. Regulation of this alternative splicing may therefore play an important role in the fine-tuning of the global level of RBMX/RBMXL1 proteins in the cells.

Keywords: Alternative splicing; B lymphocyte activation; Epstein–Barr virus; RBMXL1; Translational regulation; uORF

DOI: https://doi.org/10.1038/s41598-025-03274-3

J Agric Food Chem. 2025 Jul 03.

5'UTR Dynamics: Modulating Model Plant Defense Mechanisms against Fungal Threats.

Misbah Naz, Zhuo Chen.

Fungal pathogens threaten global crop production, causing significant yield losses and food security concerns. Understanding plant defense mechanisms against these pathogens is essential for effective disease management. The 5'-untranslated region (5'UTR) has emerged as a key regulator of immune response genes in model plants such as Arabidopsis thaliana and Nicotiana tabacum during fungal infection. The 5'UTR, traditionally linked to mRNA translation, plays a crucial role in post-transcriptional regulation of immune responses. Fungal pathogens utilize strategies like appressoria and haustoria for host penetration, prompting immune signaling via pattern recognition receptors (PRRs), which activate PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI). Recent studies show that 5'UTRs influence immune gene expression by modulating translation initiation and mRNA stability during infection. The regulatory elements are upstream open reading frames (uORFs) and RNA-binding proteins. Understanding these dynamics of novel strategies can allow the fine-tuning of immune responses, offering potential targets to improve crop disease resistance.

Keywords: 5′UTR; Arabidopsis thaliana; Nicotiana tabacum; disease; fungal pathogens; immunity

DOI: https://doi.org/10.1021/acs.jafc.5c00286

Elife. 2025 Jul 02. pii: RP105311. [Epub ahead of print]14

Human eIF2A has a minimal role in translation initiation and in uORF-mediated translational control in HeLa cells.

Mykola Roiuk, Marilena Neff, Aurelio A Teleman.

Translation initiation in eukaryotes requires a 40 S ribosome loaded with initiator tRNA which scans for an initiation codon. The initiator tRNA is usually recruited to the ribosome as part of a ternary complex composed of initiator tRNA, eIF2, and GTP. Although initiator tRNA recruitment was originally ascribed to another factor, eIF2A, it was later disproven and shown to occur via eIF2. Nonetheless, eIF2A is still considered a translation initiation factor because it binds the ribosome and shows genetic interactions with other initiation factors such as eIF4E. The exact function of eIF2A during translation initiation, however, remains unclear. Here, we use ribosome profiling and luciferase reporter assays to systematically test in HeLa cells the role of eIF2A in translation initiation, including translation of upstream ORFs. Since eIF2A is thought to take over the function of eIF2 when eIF2 is inhibited, we also test conditions where the integrated stress response is activated. In none of our assays, however, could we detect a role of eIF2A in translation initiation. It is possible that eIF2A plays a role in translation regulation in specific conditions that we have not tested here, or that it plays a role in a different aspect of RNA biology.

Keywords: biochemistry; chemical biology; developmental biology; eIF2; eIF2A; human; translation

DOI: https://doi.org/10.7554/eLife.105311