ArticleNucleic acids research2007
Modulating role of RNA structure in alternative splicing of a critical exon in the spinal muscular atrophy genes.
Article in Nucleic acids research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
126 citing papers in PubMed, 215 citations in OpenAlex.
- Evaluation of SMN protein, transcript, and copy number in the biomarkers for spinal muscular atrophy (BforSMA) clinical study.PloS one · 2012Trial
- Nusinersen: the antisense oligonucleotide at the forefront of spinal muscular atrophy treatment.RNA biology · 2026Review
- Interpretable distillation reveals that deep learning splicing models suffer from pervasive confounders and blind spots.Genome biology · 2026Article
- RNAStructuromeDB: a transcriptome-wide database of predicted RNA secondary structures with integrated APIs for functional annotation and RNA-targeted drug discovery.NAR genomics and bioinformatics · 2026Article
- Engineering B cells to express fully customizable antibodies with enhanced Fc functions.Nature communications · 2026Article
- Article
- A portable poison exon for small-molecule control of mammalian gene expression.Nature methods · 2025Article
- Engineering B cells to Express Fully Customizable Antibodies with Enhanced Fc Functions.Research square · 2025Article
- Utargetome: A targetome prediction tool for modified U1-snRNAs to identify distal-target positions with improved selectivity.PLoS computational biology · 2025Article
- Pre-mRNA Splicing Modulation by Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Identification of RNA structures and their roles in RNA functions.Nature reviews. Molecular cell biology · 2024Review
- RNA structure in alternative splicing regulation: from mechanism to therapy.Acta biochimica et biophysica Sinica · 2024Review
- A super minigene with a short promoter and truncated introns recapitulates essential features of transcription and splicing regulation of the SMN1 and SMN2 genes.Nucleic acids research · 2024Article
- Causes, functions, and therapeutic possibilities of RNA secondary structure ensembles and alternative states.Cell chemical biology · 2024Review
- U1 snRNA interactions with deep intronic sequences regulate splicing of multiple exons of spinal muscular atrophy genes.Frontiers in neuroscience · 2024Article
- Impact on splicing inRNA (New York, N.Y.) · 2023Article
- Deciphering RNA splicing logic with interpretable machine learning.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Molecular basis of RNA-binding and autoregulation by the cancer-associated splicing factor RBM39.Nature communications · 2023Article
- Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy.Nucleic acids research · 2023Article
- Base editing rescue of spinal muscular atrophy in cells and in mice.Science (New York, N.Y.) · 2023Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Humans have two nearly identical copies of the survival motor neuron (SMN ) gene, SMN1 and SMN2. Homozygous loss of SMN1 causes spinal muscular atrophy (SMA). SMN2 is unable to prevent the disease due to skipping of exon 7. Using a systematic approach of in vivo selection, we have previously demonstrated that a weak 5' splice site (ss) serves as the major cause of skipping of SMN2 exon 7. Here we show the inhibitory impact of RNA structure on the weak 5' ss of exon 7. We call this structure terminal stem-loop 2 (TSL2). Confirming the inhibitory nature of TSL2, point mutations that destabilize TSL2 promote exon 7 inclusion in SMN2, whereas strengthening of TSL2 promotes exon 7 skipping even in SMN1. We also demonstrate that TSL2 negatively affects the recruitment of U1snRNP at the 5' ss of exon 7. Using enzymatic structure probing, we confirm that the sequence at the junction of exon 7/intron 7 folds into TSL2 and show that mutations in TSL2 cause predicted structural changes in this region. Our findings reveal for the first time the critical role of RNA structure in regulation of alternative splicing of human SMN.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.