← BioTransfer GEO Dataset Finder
GEO series

Noncanonical role of ALAS1 as a heme-independent inhibitor of small RNA–mediated silencing [hepatocyte RNA-Seq]

GSE273381 Mus musculus Expression profiling by high throughput sequencing 7 samples Submitted 2024/12/19 Platform GPL21103
Summary
RNA interference (RNAi) is a fundamental strategy for gene silencing via small interfering RNAs (siRNAs) that program Argonaute (Ago) effectors, and is related to endogenous silencing via microRNAs (miRNAs). Although most efforts focus on factors that are required for miRNA/RNAi function, biological systems are typically subject to repression. Using molecular genetic approaches, we uncover ALAS1, the first enzyme in the heme biosynthesis pathway, as a repressor of miRNA accumulation in cells and in mice. This was non-intuitive, since heme is known to play a positive role as a cofactor for the nuclear miRNA processing machinery. Instead, we show that ALAS1 (but not other core heme biosynthesis factors) limits RISC assembly and activity. Notably, ALAS1 is the target of one the few current FDA-approved siRNA drugs (Givosiran). Our data have implications for side effects of Givosiran, but also for RNAi therapies in general. We provide evidence that depletion of ALAS1 enhances siRNA-mediated knockdown, suggesting that Givosiran is a viable RNAi adjuvant.
Published in
Noncanonical role of ALAS1 as a heme-independent inhibitor of small RNA-mediated silencing
Lee S, Lee S, Desnick R et al. · Science (New York, N.Y.) 2024 · PMID 39700288 · doi:10.1126/science.adp9388
This dataset
Download

Direct links to NCBI, no account and no request form: the whole study as GSE273381_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 7 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1141516 and SRA study SRP522976. Searching any of these in the dataset finder brings you back here.

Samples in this study

The sample list for this study is not cached yet. Press Sort into groups and it will be fetched from NCBI.

+ 7 more — browse all 7 samples with per-sample file links →

Similar datasets

Search all mouse RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.