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@ARTICLE{Schwarz:181955,
author = {J. D. Schwarz and S. Lukassen and P. Bhandare and L. Eing
and M. T. Snaebjörnsson$^*$ and Y. C. García and J. P.
Kisker and A. Schulze$^*$ and E. Wolf},
title = {{T}he glycolytic enzyme {ALDOA} and the exon junction
complex protein {RBM}8{A} are regulators of ribosomal
biogenesis.},
journal = {Frontiers in cell and developmental biology},
volume = {10},
issn = {2296-634X},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DKFZ-2022-02325},
pages = {954358},
year = {2022},
abstract = {Cellular growth is a fundamental process of life and must
be precisely controlled in multicellular organisms. Growth
is crucially controlled by the number of functional
ribosomes available in cells. The production of new
ribosomes depends critically on the activity of RNA
polymerase (RNAP) II in addition to the activity of RNAP I
and III, which produce ribosomal RNAs. Indeed, the
expression of both, ribosomal proteins and proteins required
for ribosome assembly (ribosomal biogenesis factors), is
considered rate-limiting for ribosome synthesis. Here, we
used genetic screening to identify novel transcriptional
regulators of cell growth genes by fusing promoters from a
ribosomal protein gene (Rpl18) and from a ribosomal
biogenesis factor (Fbl) with fluorescent protein genes (RFP,
GFP) as reporters. Subsequently, both reporters were stably
integrated into immortalized mouse fibroblasts, which were
then transduced with a genome-wide sgRNA-CRISPR knockout
library. Subsequently, cells with altered reporter activity
were isolated by FACS and the causative sgRNAs were
identified. Interestingly, we identified two novel
regulators of growth genes. Firstly, the exon junction
complex protein RBM8A controls transcript levels of the
intronless reporters used here. By acute depletion of RBM8A
protein using the auxin degron system combined with the
genome-wide analysis of nascent transcription, we showed
that RBM8A is an important global regulator of ribosomal
protein transcripts. Secondly, we unexpectedly observed that
the glycolytic enzyme aldolase A (ALDOA) regulates the
expression of ribosomal biogenesis factors. Consistent with
published observations that a fraction of this protein is
located in the nucleus, this may be a mechanism linking
transcription of growth genes to metabolic processes and
possibly to metabolite availability.},
keywords = {AldoA (Other) / RBM8A (Other) / Ribosomal protein gene
(Other) / Y14 (Other) / aldolase A (Other) / genetic screen
(Other) / genome-wide screen (Other) / ribosome biogenesis
(Other)},
cin = {A410},
ddc = {570},
cid = {I:(DE-He78)A410-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36187487},
pmc = {pmc:PMC9515781},
doi = {10.3389/fcell.2022.954358},
url = {https://inrepo02.dkfz.de/record/181955},
}