SF3B1: from core splicing factor to oncogenic driver — this #RNASpecialIssue article explores how SF3B1-mutant splicing drives cancer, with insights into prognosis, phenotypes & the need for targeted therapies. bit.ly/4bqmRy2

RNA-binding proteins in disease etiology: fragile X syndrome and spinal muscular atrophy A monthly journal publishing high-quality, peer-reviewed research on all topics related to RNA and its metabolism in all organisms

RNA-binding proteins at the crossroads of disease: Fragile X & SMA. This #RNASpecialIssue article traces how SMN complex, RNP assembly, and more emerged from curiosity-driven, collaborative RNA research. bit.ly/3Xv2hGX

Connecting genotype and phenotype in minor spliceosome diseases.
This article from the #RNASpecialIssue outlines the current structural and functional knowledge of the minor spliceosome, and discusses emerging challenges in connecting molecular dysfunctions to clinical phenotypes. bit.ly/4bt3aWz

This Perspective from the #RNASpecialIssue summarizes the current knowledge of translation dysregulation in cancer, with emphasis on the eukaryotic translation initiation factor 4F complex. It outlines recent endeavors to develop novel treatment strategies to combat cancer: bit.ly/3F4Sv8g

Adenosine-to-inosine RNA editing by ADARs, first discovered in the 1980s, plays a complex role in disease. This #RNASpecialIssue review explores current knowledge, therapeutic potential, and key unanswered questions. bit.ly/3F3Vqy1

Exploring the therapeutic potential of modulating nonsense-mediated mRNA decay.
This paper from the #RNASpecialIssue explores promising approaches employed to regulate NMD for therapeutic purposes, and highlights potential challenges in future clinical development. bit.ly/3F86Ron

Cytoplasmic regulation of the poly(A) tail length as a potential therapeutic target A monthly journal publishing high-quality, peer-reviewed research on all topics related to RNA and its metabolism in all organisms

This review from the #RNASpecialIssue discusses the distribution, regulation, and mechanisms of cytoplasmic polyadenylation element-binding proteins (CPEBs), highlighting their dual roles in either promoting or repressing gene expression depending on cellular context. bit.ly/41pFqhp

Alternative splicing (AS) is vital for heart function, and its disruption is linked to disease. This #RNASpecialIssue article highlights nonsplicing roles of AS factors and proposes a novel disease mechanism involving pathogenic RNA granules and disrupted AS factor localization. bit.ly/3DkHM9d

Cytoplasmic viruses alter nuclear trafficking, causing RNA-binding proteins (RBPs) to relocate and act as antiviral defenses. This article from the #RNASpecialIssue explores host–virus interactions and the unanswered questions about their mechanisms. bit.ly/3QJOjNG

This article examines how RNA sensors bind ligands and trigger type I interferon-stimulated genes. It also explores how mutations in RNA sensors and RNA homeostasis genes are linked to autoimmune and autoinflammatory diseases. bit.ly/4bowQEb #RNASpecialIssue

Viral quasispecies are dynamic mutant distributions that arise from high RNA replication error rates. This article from the #RNASpecialIssue reviews the molecular basis of mutant swarm formation, its role in viral disease and epidemics, and more: bit.ly/4kovSf0

RNA gain-of-function pathomechanism in DM1. Bidirec- tional transcription of DM1 DMPK produces sense CUGexp RNAs that bind MBNL proteins (red ovals), which undergo RNA–RNA, RNA–protein, and protein–protein multivalent interactions to form RNA foci or condensates (1). In contrast to sense transcription, anti- sense transcription yields very low-abundance RNAs with/without CAGexp repeats (Gudde et al. 2017). MBNL sequestration in these foci together with phosphorylated CELF (blue sphere with black P) overexpression promotes fetal splicing patterns for target RNAs in adult tissues, and in DM1 skeletal muscle, exon 7A inclusion in CLCN1 mRNA (fetal isoform) (2) results in nonsense-mediated decay (NMD), CLCN1 loss, and myotonia (3). Somatic CTG expansions result in extremely long CUGexp tracts that deplete MBNL (4) from the dilute nucleoplasmic pool, leading to release of intact or fragmented mutant DMPK mRNAs into the cytoplasm where they undergo RAN transla- tion, giving rise to toxic RAN proteins (green and brown/yellow beads) (5). Mutant DMPK antisense transcripts may be exported into the cy- toplasm at a low level, resulting in RAN translation of polyGln (Zu et al. 2011), and possibly polySer and polyAla, proteins.

This article examines RNA gain-of-function mutations from expanded short tandem repeats (STRs) in developmental and degenerative diseases. It discusses STR roles in RNA processing, their impact on myotonic dystrophy, and relevance to other STR expansion disorders: bit.ly/4igE5jS #RNASpecialIssue

Fragile X syndrome (FXS) is caused by CGG repeat expansion in FMR1, leading to DNA methylation and loss of FMRP. This #RNASpecialIssue paper explores how splice-switching ASOs and kinase inhibition can restore FMR1 expression, offering new therapeutic potential: bit.ly/4i2UpF2 #FragileX #RNAsplicing

The role of YTHDF2 in HSCs, iPSCs, AML cells, and different immune cells. (Top) The m6A/YTHDF2 influences the differentiation or proliferation of HSCs, iPSCs, and AML cells. (Bottom) YTHDF2 affects DC migration and the cross presentation of antitumoral macrophages and maintains the suppressive function of MDSCs and Tregs. In general, inhibiting YTHDF2 triggers the antitumor immunity. Figure created with BioRender.

YTHDF2, a key m6A reader, regulates the m6A-modified epitranscriptome in development, stem cell expansion, and immune evasion. This #RNASpecialIssue review explores its mechanisms and therapeutic potential in cancer treatment. Read more: bit.ly/4knZut8

Mitochondrial (mt-) tRNA modifications play pivotal roles in decoding and sustaining tRNA stability. Loss of mt-tRNA modifications can result in mitochondrial dysfunctions and diseases.

Modifications of mitochondrial tRNA (mt-tRNA) are crucial for decoding and stabilizing tRNA. This review from the #RNASpecialIssue examines their roles in disease and emerging therapies. bit.ly/3EYriE3

Pictorial representation of a viral quasispecies as the background of a complex virosphere embedded in a diverse cellular world.

The RNA Journal Special Issue on RNA & Disease highlights how subtle RNA changes, modifications, and interactions drive pathology across organs and systems. This month, look out for 15 articles spanning diverse topics, from molecular mechanisms to therapeutic insights. #RNASpecialIssue