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Published October 2012 | Published + Supplemental Material
Journal Article Open

Nutritional control of mRNA isoform expression during developmental arrest and recovery in C. elegans

Abstract

Nutrient availability profoundly influences gene expression. Many animal genes encode multiple transcript isoforms, yet the effect of nutrient availability on transcript isoform expression has not been studied in genome-wide fashion. When Caenorhabditis elegans larvae hatch without food, they arrest development in the first larval stage (L1 arrest). Starved larvae can survive L1 arrest for weeks, but growth and post-embryonic development are rapidly initiated in response to feeding. We used RNA-seq to characterize the transcriptome during L1 arrest and over time after feeding. Twenty-seven percent of detectable protein-coding genes were differentially expressed during recovery from L1 arrest, with the majority of changes initiating within the first hour, demonstrating widespread, acute effects of nutrient availability on gene expression. We used two independent approaches to track expression of individual exons and mRNA isoforms, and we connected changes in expression to functional consequences by mining a variety of databases. These two approaches identified an overlapping set of genes with alternative isoform expression, and they converged on common functional patterns. Genes affecting mRNA splicing and translation are regulated by alternative isoform expression, revealing post-transcriptional consequences of nutrient availability on gene regulation. We also found that phosphorylation sites are often alternatively expressed, revealing a common mode by which alternative isoform expression modifies protein function and signal transduction. Our results detail rich changes in C. elegans gene expression as larvae initiate growth and post-embryonic development, and they provide an excellent resource for ongoing investigation of transcriptional regulation and developmental physiology.

Additional Information

© 2012 by Cold Spring Harbor Laboratory Press. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/. Received October 18, 2011; Accepted April 24, 2012. Published in Advance April 26, 2012. We thank Lisa Bukovnik and Nick Hoang of the Duke IGSP Genome Sequencing and Analysis Core Resource. This work was supported by the Ellison Medical Foundation and the National Science Foundation (IOS-1120206).

Attached Files

Published - Genome_Res.-2012-Maxwell-1920-9.pdf

Supplemental Material - Maxwell_Sup_Fig1.tif

Supplemental Material - Maxwell_Sup_Fig2.pdf

Supplemental Material - Maxwell_Sup_Fig3.pdf

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Supplemental Material - Maxwell_Sup_Fig5.pdf

Supplemental Material - Maxwell_Sup_Fig6.pdf

Supplemental Material - Supp_Info.doc

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