🚨 Another preprint from the lab out today! 🚨
This work led by former trainee Dr. Juan Brado @the-te-guy.bsky.social and new grad student Ms. Eyael Tewelde, to undertstand how upregulation of a single retrotransposon (here, AluJB) impacts cellular phenotypes! A 🧵, 1/9
www.biorxiv.org/content/10.1...

This study started with a simple question: could #age-related upregulation of #TEs (without "jumping") be enough to shape cell health?
We thus set out to identify candidate elements, using a catalog of human fibroblast gene expression with #aging, revealing #AluJB as a candidate. 2/9

We also performed functional assays to validate our omic findings, and found that indeed, AluJb-overexpressing fibroblasts show remodeled mitochondria metabolism, S-phase accumulation/replication stalling and decreased aggresome load. 3/4

Here, we show that overexpression of AluJb, a transposition-incompetent SINE, in human fibroblasts, leads to profound remodeling of transcriptome, proteome and secretome. Intriguingly, many AluJb-regulated pathways correspond to aging hallmarks (i.e. mitochondria, proteostasis, self-renewal). 2/4

Together, our data shows that increased transcriptional levels of #AluJB are sufficient to drive changes in many cellular processes related to the #hallmarks of #aging - thus suggesting that #TE derepression may exert causal effects on the #aging process rather than be a mere bystander. 8/9

This led us to #functionally test whether these processes were directly impacted in IMR90 fibroblasts overexpressing #AluJB. Consistent with omic predictions, we observed decreased #respiratory rates, #S-phase accumulation and changes in #aggresome load! 7/9

Thus, we decided to overexpress #AluJB in primary IMR90 fibroblasts, and perform multi-omic profiling of its impact on the #transcriptome, #proteome and #secretome. We were surprised to see large scale multi-omic remodeling in response to #AluJB. 4/9

Intriguingly, higher endogenous #AluJB transcriptional levels were associated with enrichments of pathways related to #aging #hallmarks, including #proteostasis, cell cycle and #ECM remodeling. 3/9

É. O Corinthians perdeu no último minuto.
O Xandão tá olhando pra ordem de prisão como aquele gato vilão seduzido pela chama

youtube.com/shorts/alUJB...