Post-transcriptional regulation
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   Post-transcriptional control of gene expression is important for cellular functions across biological contexts. Earliest stages of animal development occur in the absence of transcription, which offers a unique context to study specifically post-transcriptional mechanisms of gene regulation. Using zebrafish, and Xenopus, as a model organisms we use functional genomics to understand the post-transcriptional regulatory code in vertebrates. Our efforts span investigating RNA stability, RNA modifications, RNA structure, RNA binding proteins and their recognition sequences, upstream ORFs, non-coding RNAs, and translation regulation. We aim to understand the role for these regulatory features during embryonic development to gain insight into how a single cell gives rise to a multicellular organism.

zygotic

maternal

miR-430

RNA Binding Proteins

Codon usage/ribosome

Top: central dogma of molecular biology adapted to the maternal-to-zygotic transition. Currently we do not know what factors clear the maternal mRNAs (Y) and activate the zygotic transition (X)

Example of mRNAs that are cleared during the maternal to zygotic transition by different pathways. (Carter Takacs, Valeria Yartseva)


       Figure: We have developed a method to determine the regulatory activity of RNA fragments in the 3‘UTR and the coding sequences, that we term RASA-seq. (RNA stability assay). This has allowed us to map regulatory sequences across the transcriptome in a quantitative manner.

Furthermore we have developed methods to probe the structure of the RNA,  the function of individual RNA fragments in the transcriptome, and the proteins bound to the RNA. Combining iClip with motif discovery algorithms we are defining the regulatory network of proteins that recognize specific sequences and structures to regulate mRNA stability and translation.We have also recently found an important role for translation and the ribosome in the regulation of mRNA stability and Translational regulation.


Using this information we are using machine learning algorithms to integrate each of the regulatory inputs mentioned above to model gene expression during developmental transitions across species.


    Finally, we aim to understand the role for each of those elements on the making of an embryo, so we are capitalizing to the improvemenst on crispr technology to mutagenize these elements and understand their function in development.

    Our starting point to investigate the post-transcriptional regulatory code is the maternal to zygotic transition, a universal developmental transition across animal development where thousands of mRNAs are post-transcriptionally regulated. While microRNAs play a role in this regulation, these can only explain ~20% of the regulation that takes place and  we are currently investigating how translation by the ribosome, RNA binding proteins and non-coding RNAs regulate mRNAs for decay.

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