Biology subjects

Moradi Fard, S.

Publications and source records attributed to Moradi Fard, S..

3 recordsLinked to original sources

bioRxiv2023

Intrinsic disorder specifies discreet functions of nucleoplasmin-like histone chaperones

Nucleoplasmin (NPM) histone chaperones regulate distinct processes in the nucleus and nucleolus. While intrinsically disordered regions (IDRs) are hallmarks of NPMs, it is not clear if all NPM functions require these unstructured features. We assessed the importance of IDRs in yeast NPM-like proteins and found that regulation of rDNA copy number, and genetic interactions with the nucleolar RNA surveillance machinery require the highly conserved FKBP prolyl isomerase domain, but not the NPM domain or IDRs. By contrast, transcriptional silencing in the nucleus requires IDRs. We demonstrate that multiple lysines in poly-acidic serine/lysine motifs of IDRs are required for both lysine polyphosphorylation and NPM-mediated transcriptional silencing. These results demonstrate that NPM-like proteins do not rely on IDRs for all chromatin-related functions.

molecular biology↗

bioRxiv2022

SIR telomere silencing depends on nuclear envelope lipids and modulates sensitivity to a lysolipid drug

The nuclear envelope (NE) is important in maintaining genome organization. The role of lipids in the communication between the NE and telomere silencing was investigated, including how changes in lipid composition impact gene expression and overall nuclear architecture. For this purpose, yeast cells were treated with the non-metabolizable lysophosphatidylcholine analog edelfosine, known to accumulate at the perinuclear endoplasmic reticulum. Edelfosine treatment induced NE deformation and disrupted telomere clustering but not anchoring. In addition, the association of Sir4 at telomeres measured by ChIP decreased. RNA-seq analysis showed altered expression of Sir-dependent genes located at sub-telomeric (0-10 kb) regions, which was consistent with Sir4 dispersion. Transcriptomic analysis revealed that two lipid metabolic circuits were activated in response to edelfosine, one mediated by the membrane sensing transcription factors, Spt23/Mga2, and the other by a transcriptional repressor, Opi1. Activation of these combined transcriptional programs resulted in higher levels of unsaturated fatty acids and the formation of nuclear lipid droplets. Interestingly, cells lacking Sir proteins displayed resistance to unsaturated fatty acids and edelfosine, and this phenotype was connected to Rap1. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=65 SRC="FIGDIR/small/499406v3_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@a46borg.highwire.dtl.DTLVardef@2a7f44org.highwire.dtl.DTLVardef@95ceforg.highwire.dtl.DTLVardef@b4678c_HPS_FORMAT_FIGEXP M_FIG C_FIG SummaryThe nuclear envelope (NE) is important for nuclear organization. This study shows that changes in NE lipid composition from lysolipid treatment decreases Sir4 association with telomeres, their clustering at NE, and triggers lipid-specific transcriptional circuits regulated by membrane-sensing factors.

molecular biology↗

bioRxiv2020

A Fob1 independent role for the Smc5/6 complex in the rDNA that modulates lifespan.

The ribosomal DNA (rDNA) in Saccharomyces cerevisiae is in one tandem repeat array on Chromosome XII. Two spacer regions within each repetitive element, called non-transcribed spacer 1 (NTS1) and NTS2, are important in nucleolar organization. Smc5/6 localizes to both NTS1 and NTS2 and is involved in the regulation of Sir2 and Cohibin binding at NTS1, whereas Fob1 and Sir2 are required for optimal binding of the complex to NTS1 and NTS2, respectively. We demonstrate that Smc5/6 functions in chromatin silencing at NTS1 independently of its role in homologous recombination (HR) when forks pause at the replication fork barrier (RFB). In contrast, when the complex does not localize to the rDNA in nse3-1 mutants, the shortened lifespan correlates with NTS2 homeostasis independently of FOB1 status. Our data identify the importance of Smc5/6 integrity in NTS2 transcriptional silencing and repeat tethering, which in turn underscores rDNA stability and replicative lifespan. HighlightsO_LISmc5/6 is important for transcriptional silencing in the rDNA. C_LIO_LISmc5/6 tethers the rDNA array to the periphery. C_LIO_LITranscriptional silencing of ncRNA at NTS1 and NTS2 is differentially regulated. C_LIO_LISmc5/6 has a role in rDNA maintenance independent of HR processing at the RFB. C_LIO_LIFob1-independent disruption of Smc5/6 at NTS2 leads to lifespan reduction. C_LI

molecular biology↗