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Godoy Herz, M. A.

Publications and source records attributed to Godoy Herz, M. A..

3 recordsLinked to original sources

Microexon alternative splicing and feeding behavior in C. elegans.

Microexons are short alternative exons up to 51 nucleotides long that are highly enriched in neuronal genes. Their dysregulation has been linked to human neurodevelopmental disorders, including autism spectrum disorders. In the nematode Caenorhabditis elegans, global regulation of microexons is also critical for proper development. Here we show that microexon alternative splicing (AS) changes between C. elegans larval and adult stages and that microexon inclusion is differentially regulated among distinct neuronal types. Consistently with previous evidence that C. elegans splicing is regulated in response to environmental stimuli, we found here that specific microexons are modulated upon food availability. Both the inclusion levels of these microexons and the feeding behavior seem to depend on the DNA topology, which may affect transcription dynamics, as revealed by the effects of the topoisomerase I (TOP1) inhibitor, camptothecin (CPT). CPT treatment alters responses related to food availability such as speed reduction and exploration. Furthermore, animals carrying a mutation in the global regulator of microexon splicing prp-40 exhibit altered food preference, independently demonstrating that disruption of microexon AS has important consequences on animal behavior.

molecular biology↗

Light regulates widespread plant alternative polyadenylation through the chloroplast

Transcription of eukaryotic protein-coding genes generates immature mRNAs that are subjected to a series of processing events, including capping, splicing, cleavage and polyadenylation (CPA) and chemical modifications of bases. Alternative polyadenylation (APA) greatly contributes to mRNA diversity in the cell. By determining the length of the 3 untranslated region, APA generates transcripts with different regulatory elements, such as miRNA and RBP binding sites, which can influence mRNA stability, turnover and translation. In the model plant Arabidopsis thaliana, APA is involved in the control of seed dormancy and flowering. In view of the physiological importance of APA in plants, we decided to investigate the effects of light/dark conditions and compare the underlying mechanisms to those elucidated for alternative splicing (AS). We found that light controls APA in approximately 30% of Arabidopsis genes. Similar to AS, the effect of light on APA requires functional chloroplasts, is not affected in mutants of the phytochrome and cryptochrome photoreceptor pathways and is observed in roots only when the communication with the photosynthetic tissues is not interrupted. Furthermore, mitochondrial activity is necessary for the effect of light in roots but not in shoots. However, unlike AS, coupling with transcriptional elongation does not seem to be involved since light-dependent APA regulation is neither abolished in mutants of the TFIIS transcript elongation factor nor universally affected by chromatin relaxation caused by the histone deacetylase inhibition. Instead, regulation seems to be linked to light-elicited changes in the abundance of constitutive CPA factors, also mediated by the chloroplast.

molecular biology↗

Remote control of alternative splicing in roots through TOR kinase

For plants, light is the source of energy and the most relevant regulator of growth and adaptations to the environment by inducing changes in gene expression at various levels, including alternative splicing. Chloroplasts trigger retrograde signals that control alternative splicing in leaves and roots in response to light. Here we provide evidence suggesting that sugars, derived from photosynthesis, act as mobile signals controlling alternative splicing in roots. The inhibition of TOR kinase activity diminishes the alternative splicing response to light and/or sugars in roots, showing the relevance of the TOR pathway in this signaling mechanism. Furthermore, disrupting the function of the mitochondria abolishes alternative splicing changes supporting a key role for these organelles in this signaling axis. We conclude that sugars can act as mobile signals coordinating alternative splicing responses to light throughout the whole plant, exerting this function in roots by activating the TOR pathway.\n\nGraphical Abstract\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC=\"FIGDIR/small/472126v2_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (76K):\norg.highwire.dtl.DTLVardef@a8c978org.highwire.dtl.DTLVardef@1430da0org.highwire.dtl.DTLVardef@1339990org.highwire.dtl.DTLVardef@a6dd5a_HPS_FORMAT_FIGEXP M_FIG C_FIG Art by Dr. Luciana Giono.

molecular biology↗