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Joana Vidigal

@vidigaljoana.bsky.social

1K followers 240 following 43 posts

Studying small RNAs and Argonaute proteins in mammals using mouse genetics. Part time runner, full time mom of Best Kiddo Ever (BKE) https://ccr.cancer.gov/staff-directory/joana-a-vidigal

ccr.cancer.gov

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Joana Vidigal @vidigaljoana.bsky.social · Apr 4

What was that you said? You are looking for new #RNA research to read in the weekend?

You are in luck!

📣 📣 Check out the new preprint from our lab!!!! 📣 📣

www.biorxiv.org/content/10.1...

AGO2 slicing of a domesticated retrotransposon is necessary for normal vasculature development

Argonaute (AGO) mediated slicing of RNA, also known as RNAi, is a highly conserved phenomenon that is evolutionarily linked to the repression of transposons and other repeats. Although RNAi is no long...

www.biorxiv.org

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Reposted by Joana Vidigal

Pedro Rocha @pedroprocha.bsky.social · Sep 8

🚨🚨🚨 Please repost
We are looking for postdocs to join our lab at NIH.
Apply:
www.nichd.nih.gov/research/atNICHD/Investigators/rocha/apply
Learn more about training at NIH :
www.training.nih.gov/research-tra...

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Reposted by Joana Vidigal

Sandra Wolin @slwolin.bsky.social · Aug 1

A giant thank you to @drjz.bsky.social and @vidigaljoana.bsky.social! It takes a village to celebrate #RNAday

Joe Ziegelbauer @drjz.bsky.social · Aug 1

NIH had fun celebrating another #RNAday. Thanks to @vidigaljoana.bsky.social for organizing this great event and @slwolin.bsky.social for building a strong RNA community.

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Reposted by Joana Vidigal

Joe Ziegelbauer @drjz.bsky.social · Aug 1

NIH had fun celebrating another #RNAday. Thanks to @vidigaljoana.bsky.social for organizing this great event and @slwolin.bsky.social for building a strong RNA community.

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Reposted by Joana Vidigal

Jackson Hoffman @jxhoffman.bsky.social · Feb 12

Unpause! I'm super happy to now be able to share the published version of our paper at Science Advances showing that:
1) active histone mods occur independently of transcription
2) transcription coordinates histone deacetylation at active promoters
www.science.org/doi/10.1126/...

RNA polymerase II coordinates histone deacetylation at active promoters

Transcription initiation limits histone acetylation and H2AZ incorporation at promoters.

www.science.org

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Reposted by Joana Vidigal

ktr-nakanishi.bsky.social @ktr-nakanishi.bsky.social · May 6

My research group seeks a highly motivated Post-Bacc (or Tech). This position offers a unique opportunity to contribute to research on cleavage-inducing tiny RNAs (cityRNAs) to treat neurological and neuromuscular disorders, Cancer, Alzheimer's diseases, etc.
u.osu.edu/cbcundergrad...

Job Opportunity for Recent Graduates (Post-Bacc) | CBC Undergraduate Program

u.osu.edu

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Reposted by Joana Vidigal

Nelson Lau Lab @nelson-lau-lab.bsky.social · Apr 11

Why NIH/NIGMS funding of basic research matters with our latest work now out in @cp-cellreports.bsky.social sky.social. We solved a >30-year-old mystery of what transcription factor drives the Flamenco piRNA cluster required for female Drosophila fertility. /1
www.cell.com/cell-reports...

Traffic Jam activates the Flamenco piRNA cluster locus and the Piwi pathway to ensure transposon silencing and Drosophila fertility

Rivera et al. discover Drosophila Flamenco piRNA cluster enhancers bound and activated by the Traffic Jam transcription factor. Traffic Jam also binds many follicle cell genes including activating mul...

www.cell.com

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Joana Vidigal @vidigaljoana.bsky.social · Apr 5

Thanks Eric!

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

Thanks Jay!

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

Thanks a lot Josh!

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

Together, our data show that Rtl1 is an essential mRNA cleavage target of AGO2 and suggest that the repurposing of a retrotransposon-Argonaute regulatory interaction contributed to the retention of AGO catalytic competence in mammals

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

And finally, if we restore silencing of Rtl1 in mutant endothelial cells, we can essentially rescue all the endothelial phenotypes we documented!

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

It is also an imprinted gene, expressed only from the paternal allele. The maternal allele expresses instead a cluster of miRNAs that overlap Rtl1 in an antisense manner.

And you guessed it: we can find Rtl1 cleavage products for these miRNAs in RNA from wild-type but not catalytic mutant animals

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

Who is Rtl1? It turns out it is a domesticated retrotransposon known to regulate endothelial cell function - these are the cells that line our vessels

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

Turns out that one of the up-regulated genes, Rtl1, has 10 (!!!) perfect binding sites for well-expressed miRNAs! 😱

This extent of complementarity is well known to trigger RNA cleavage by AGO2

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

This is also pretty obvious in expression profiles from these animals, which show numerous genes up-regulated, which are largely involved vasculature development

a volcano plot on the left shows genes dysregulated in Ago2 mutants, plot on the right shows enrichment of GO terms

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

It turns out, there a lot more wrong with these animals than just anemia (check out the paper for all the things we found!)

For one thing, these animals have extensive vascular defects characterized by enlarged and leaky vessels

immunofluorescence to CD31 endothelial cell marker shows enlarged fetal vessels in catalytic mutant animals, which is quantified on the right

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

So clearly there are other important cleavage targets in mammals.

We set out to find who they were!

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

These are so far the only cleavage targets in mammals whose dysregulation was shown to cause phenotypes in AGO2 catalytic dead mice - a very strong anemia

And yet.... these animals also die a few hours after birth! For unknown reasons!

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

we know from work in the Hannon and @lucksmith.bsky.social's labs that that AGO2 slicing is required for erythrocyte differentiation by promoting the maturation of 2 unusual miRNAs:

pubmed.ncbi.nlm.nih.gov/20424607/
pubmed.ncbi.nlm.nih.gov/29351846/

A dicer-independent miRNA biogenesis pathway that requires Ago catalysis - PubMed

The nucleolytic activity of animal Argonaute proteins is deeply conserved, despite its having no obvious role in microRNA-directed gene regulation. In mice, Ago2 (also known as Eif2c2) is uniquely req...

pubmed.ncbi.nlm.nih.gov

Joana Vidigal @vidigaljoana.bsky.social · Apr 4

It is fair to say that we have been obsessed with mammalian Argonaute proteins in the lab, and particularly the ability of AGO2 to slice transcripts!

This activity is incredibly conserved, and yet we have a poor understanding of what it's regulatory functions are in mammals 🤔