Abstract
Zebrafish are able to regenerate heart muscle after catastrophic injury. Fervent research is underway to discover critical molecules with therapeutic potential, yet many principal biological processes that underlie regeneration likely remain undiscovered. Changes in the abundance of dozens to thousands of mRNA have been reported using both targeted approaches like in-situ hybridization and unbiased approaches like RNA-seq. However, whether the abundance of mRNA represents the entirety of gene expression control remains unknown. Regulation of translation may alter the abundance of a critical protein product without requiring an intervening transcription event. Here, we have taken advantage of ribosome profiling to document the changes in translation efficiency that accompany heart regeneration. Using high-throughput sequencing of the ~28 nucleotide fragments of mRNA protected from enzymatic degradation, we find thousands of transcripts that change in their association with ribosomes. We also find that key components of the translational machinery are transcriptionally induced during regeneration, supporting a general model in which regulation of translation is a fundamental component of zebrafish heart regeneration.
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