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Microexons (≤27 nt) play critical roles in nervous system development and function but create unique challenges for the splicing machinery. The mechanisms of microexon regulation are therefore of great interest. We performed a genetic screen for alternative splicing regulators in the C. elegans nervous system and identify PRP-40, a core component of the U1 snRNP. RNA-seq reveals that PRP-40 is required for inclusion of alternatively spliced, but not constitutively spliced, exons. PRP-40 is particularly required for inclusion of neuronal microexons, and our data indicate that PRP-40 is a central regulator of microexon splicing. Microexons can be relieved from PRP-40 dependence by artificially increasing exon size or reducing flanking intron size, indicating that PRP-40 is specifically required for microexons surrounded by conventionally sized introns. Knockdown of the orthologous PRPF40A in mouse neuroblastoma cells causes widespread dysregulation of microexons but not conventionally sized exons. PRP-40 regulation of neuronal microexons is therefore a widely conserved phenomenon.
Pubmed ID: 34348142
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Suite of motif-based sequence analysis tools to discover motifs using MEME, DREME (DNA only) or GLAM2 on groups of related DNA or protein sequences; search sequence databases with motifs using MAST, FIMO, MCAST or GLAM2SCAN; compare a motif to all motifs in a database of motifs; associate motifs with Gene Ontology terms via their putative target genes, and analyze motif enrichment using SpaMo or CentriMo. Source code, binaries and a web server are freely available for noncommercial use.
View all literature mentionsSoftware platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.
View all literature mentionsCollection of curated, non-redundant genomic DNA, transcript RNA, and protein sequences produced by NCBI. Provides a reference for genome annotation, gene identification and characterization, mutation and polymorphism analysis, expression studies, and comparative analyses. Accessed through the Nucleotide and Protein databases.
View all literature mentionsWeb server for functional enrichment analysis and conversions of gene lists. Web based tool for functional profiling of gene lists from large scale experiments. Has web interface with powerful visualization. Used for analyzing data from any organism.
View all literature mentionsSoftware performing alignment of high-throughput RNA-seq data. Aligns RNA-seq reads to reference genome using uncompressed suffix arrays.
View all literature mentionsCenter that acquires, maintains, and distributes genetic stocks and information about stocks of the small free-living nematode Caenorhabditis elegans for use by investigators initiating or continuing research on this genetic model organism. A searchable strain database, general information about C. elegans, and links to key Web sites of use to scientists, including WormBase, WormAtlas, and WormBook are available.
View all literature mentionsA generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms.
View all literature mentionsThis monoclonal targets dsRed, mRFP, mCherry , mPlum, mRFPruby
View all literature mentionsThis monoclonal targets dsRed, mRFP, mCherry , mPlum, mRFPruby
View all literature mentionsThis monoclonal targets GFP
View all literature mentionsThis polyclonal targets GFP
View all literature mentionsCell line Neuro-2a is a Cancer cell line with a species of origin Mus musculus
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