Vaknin, I. | Search bioRxiv

bioRxiv2026

RTTN moonlights beyond the centrosome to control ribosome biogenesis and tRNA modification in human brain organoids

RTTN (rotatin) is a centrosomal protein mutated in severe malformations of cortical development, yet how its dysfunction disrupts human corticogenesis has remained unclear. Here, we show that RTTN has an unrecognized function at the core of the translation machinery. Using human telencephalic and hippocampal organoids carrying distinct RTTN alleles, together with single-cell and bulk transcriptomics, polysome profiling, and tRNA pseudouridine sequencing, we find that RTTN is enriched in cycling first-trimester neural progenitors and physically associates with ribosome-biogenesis and RNA-processing factors. RTTN mutations impair rRNA biogenesis and polysome assembly, reduce cytoplasmic ribosome density and nascent protein synthesis, and remodel the tRNA pseudouridylation landscape through both a PUS7L-dependent variable-arm signature and a broader RTTN-specific defect. These translational deficits are accompanied by prolonged mitosis, reduced entry into S-phase, and impaired interkinetic nuclear migration in mutant progenitors. Our findings redefine RTTN as a regulator of ribosome homeostasis and mRNA translation and implicate defective translational capacity as a driver of RTTN-associated microcephaly. Graphical AbstractRTTN sustains ribosome and tRNA homeostasis in human neural progenitors; its mutation disrupts mRNA translation, stalling progenitor proliferation and interkinetic nuclear migration, and driving cortical malformation and growth failure. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/744412v1_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@16124aaorg.highwire.dtl.DTLVardef@ae23f7org.highwire.dtl.DTLVardef@bb588forg.highwire.dtl.DTLVardef@1b35028_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2018

Improved DNA based storage capacity and fidelity using composite DNA letters

DNA, with its remarkable density and long-term stability, is an appealing potential next generation data storage medium, most notably for long-term archiving. Megabyte scale DNA based storage was first reported in 2012. The Shannon information capacity of DNA was recently demonstrated, using fountain codes, to be [~]1.57 bit per synthesized position. However, synthesis and sequencing technologies process multiple nominally identical molecules in parallel, leading to significant information redundancies. We introduce composite DNA alphabets, using mixed DNA base types, to leverage this redundancy, enabling higher density. We develop encoding and decoding for composite DNA based storage, including error correction. Using current DNA synthesis technologies, we code 6.4 Megabyte data into composite DNA, achieving [~]25% increase in capacity as compared to literature. We further demonstrate, on smaller scales, how flexible synthesis leads to 2.7 fold increased capacity per synthesized position. Composite DNA can thus reduce costs for DNA based storage and can also serve in other applications.

synthetic biology↗