Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 53,026 bioRxiv papers from 245,564 authors.

A post-transcriptional regulatory code for mRNA stability during the zebrafish maternal-to-zygotic transition

By Charles E Vejnar, Mario Abdel Messih, Carter M Takacs, Valeria Yartseva, Panos Oikonomou, Romain Christiano, Marlon Stoeckius, Stephanie Lau, Miler T Lee, Jean-Denis Beaudoin, Hiba Darwich-Codore, Tobias C Walther, Saeed Tavazoie, Daniel Cifuentes, Antonio J Giraldez

Posted 30 Mar 2018
bioRxiv DOI: 10.1101/292441

Post-transcriptional regulation is crucial to shape gene expression. During the Maternal-to-Zygotic Transition (MZT), thousands of maternal transcripts are regulated upon fertilization and genome activation. Transcript stability can be influenced by cis-elements and trans-factors, but how these inputs are integrated to determine the overall mRNA stability is unclear. Here, we show that most transcripts are under combinatorial regulation by multiple decay pathways during zebrafish MZT. To identify cis-regulatory elements, we performed a massively parallel reporter assay for stability-influencing sequences, which revealed that 3'-UTR poly-U motifs are associated with mRNA stability. In contrast, miR-430 target sequences, UAUUUAUU AU-rich elements (ARE), CCUC and CUGC elements emerged as the main destabilizing motifs in the embryo, with miR-430 and AREs causing mRNA deadenylation in a genome activation-dependent manner. To identify the trans-factors interacting with these cis-elements, we comprehensively profiled RNA-protein interactions and their associated regulatory activities across the transcriptome during the MZT. We find that poly-U binding proteins are preferentially associated with 3'-UTR sequences and stabilizing motifs, and that antagonistic sequence contexts for poly-C and poly-U binding proteins shape the binding landscape and magnitude of regulation across the transcriptome. Finally, we integrate these regulatory motifs into a machine learning model that accurately predicts the stability of mRNA reporters in vivo. Our findings reveal how mechanisms of post-transcriptional regulation are coordinated to direct changes in mRNA stability within the early zebrafish embryo.

Download data

  • Downloaded 986 times
  • Download rankings, all-time:
    • Site-wide: 5,897 out of 53,026
    • In genomics: 993 out of 3,782
  • Year to date:
    • Site-wide: 7,195 out of 53,026
  • Since beginning of last month:
    • Site-wide: 7,098 out of 53,026

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide

Sign up for the Rxivist weekly newsletter! (Click here for more details.)