Biology subjects

Rong, Y. S.

Publications and source records attributed to Rong, Y. S..

3 recordsLinked to original sources

bioRxiv2025

Angel Wing: a class of alternative splicing regulators in animals

Alternative splicing (AS) regulates the diversity and level of the proteome. The specificity in AS is in turn regulated by RNA binding proteins, but our understanding of how they act is far from complete. Here we identify the Angel wing (Anw) protein as a novel AS regulator. Loss of Anw in Drosophila disrupts splicing in muscle genes and subsequently muscle function. Based on a mini-gene assay in which Anw and its RNA targets are co-expressed in cultured cells, we demonstrated orthologous splicing regulation of the minigene transcripts, interaction between Anw and its RNA targets, and a remarkable functional conservation among Anw homologs. Anw forms nuclear foci, and genetic ablation of Anw domains suggests that maintaining distinctive features of these foci is important for its function. The evolution of Anw is dynamic with gene gains and losses, but preserves a cross-phyla "ultra conserved element" as an alternative exon that potentially regulates its own level by non-sense mediated mRNA decay. As the human anw homolog is a candidate gene for myasthenia gravis, our work suggests a mechanism for cellular dysfunction in this disease.

genetics↗

bioRxiv2024

The Ptch methylase installs an m3U modification on 28S rRNA for efficient protein synthesis in flies and men

The ribosomal RNA (rRNA) is one of the most heavily modified RNA species in nature. Although we have advanced knowledge of the sites, functions and the enzymology of many of the rRNA modifications from all kingdoms, we lack basic understanding on many of those that are not universally present. A single N3 modified Uridine base (m3U) was identified on the 28S rRNA from human and frog over thirty years ago, which is absent in bacteria or yeast. Here we show that the equivalent m3U is present in Drosophila, and that the Ptch enzyme and its human homolog are both necessary and sufficient for carrying out the modification. The Ptch-modified U is at a functional center of the large ribosome, and consistently ptch-mutant cells suffer loss of ribosomal functions. Ptch, proposed to be the most druggable RNA methyltransferases in human, represents a unique target where ribosomal functions could be specifically compromised in cancer cells.

genetics↗

bioRxiv2023

Drosophila Amus and Bin3 methylases functionally replace mammalian MePCE for capping and the stabilization of U6 and 7SK snRNAs

U6 and 7SK snRNAs process a 5 cap, believed to be essential for their stability and maintained by mammalian MePCE or Drosophila Bin3 enzymes. Although loss of either protein results in 7SK instability, loss of neither is associated with U6 reduction. Their yeast homolog is also not required for U6 stability, casting further doubts on the function of capping U6. Here we show that the Drosophila Amus protein, homologous to both Bin3 and MePCE, is essential for U6 but not 7SK stability. A full function of Amus is required for Drosophila development, and that rests primarily on Amuss methylase activity. Remarkably, the loss of U6 is rescued by the expression of an Amus-MePCE hybrid protein harboring the methyltransferase domain from MePCE, highlighting the conserved function of the two proteins as the U6 capping enzyme. Our new investigations in human cells establish a dependence of both U6 and 7SK stability on MePCE, resolving a long-standing uncertainty. While uncovering an interesting division of labor of Bin3/MePCE/Amus proteins, we discovered a "Bin3-Box" domain present only in enzymes associated with 7SK regulation. Targeted mutagenesis in Drosophila confirmed its importance for Bin3 function, revealing a possible conserved element in 7SK but not U6 biology.

genetics↗