In Drosophila, the global increase in transcription from the male X chromosome to compensate for its monosomy is mediated by the male-specific lethal (MSL) complex consisting of five proteins and two non-coding RNAs, roX1 and roX2. After an initial sequence-dependent recognition by the MSL complex of 150-300 high affinity sites, the spread to the majority of the X-linked genes depends on local MSL-complex concentration and active transcription. We have explored whether any additional RNA species are associated with the MSL complex. No additional roX RNA species were found, but a strong association was found between a spliced and poly-adenylated msl2 RNA and the MSL complex. Based on our results, we propose a model in which a non-chromatin-associated partial or complete MSL-complex titrates newly transcribed msl2 mRNA and thus regulates the amount of available MSL complex by feedback. This represents a novel mechanism in chromatin structure regulation.
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http://dx.doi.org/10.1093/nar/gkr236 | DOI Listing |
Nat Commun
January 2025
Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, Key Laboratory of Quantitative Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
Elife
December 2024
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russian Federation.
The male-specific lethal complex (MSL), which consists of five proteins and two non-coding roX RNAs, is involved in the transcriptional enhancement of X-linked genes to compensate for the sex chromosome monosomy in XY males compared with XX females. The MSL1 and MSL2 proteins form the heterotetrameric core of the MSL complex and are critical for the specific recruitment of the complex to the high-affinity 'entry' sites (HAS) on the X chromosome. In this study, we demonstrated that the N-terminal region of MSL1 is critical for stability and functions of MSL1.
View Article and Find Full Text PDFMol Diagn Ther
November 2024
Divisions of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Colorado Denver, Anschutz Medical Campus, 12700 East 19th Avenue, MS 8613, Aurora, CO, 80045, USA.
To better understand ovarian cancer lethality and treatment resistance, sophisticated computational approaches are required that address the complexity of the tumor microenvironment, genomic heterogeneity, and tumor evolution. The ovarian cancer tumor ecosystem consists of multiple tumors and cell types that support disease growth and progression. Over the last two decades, there has been a revolution in -omic methodologies to broadly define components and essential processes within the tumor microenvironment, including transcriptomics, metabolomics, proteomics, genome sequencing, and single-cell analyses.
View Article and Find Full Text PDFBiophys Chem
January 2025
Molecular Systems Biology Unit, European Molecular Biology Laboratory (EMBL), 69117 Heidelberg, Germany; Department of Biochemistry IV - Biophysical Chemistry, University of Bayreuth, 95447 Bayreuth, Germany. Electronic address:
Repression of msl-2 mRNA translation is essential for viability of Drosophila melanogaster females to prevent hypertranscription of both X chromosomes. This translational control event is coordinated by the female-specific protein Sex-lethal (Sxl) which recruits the RNA binding proteins Unr and Hrp48 to the 3' untranslated region (UTR) of the msl-2 transcript and represses translation initiation. The mechanism exerted by Hrp48 during translation repression and its interaction with msl-2 are not well understood.
View Article and Find Full Text PDFBiochim Biophys Acta Rev Cancer
November 2024
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Weijin Road, Tianjin 300072, China. Electronic address:
Cancer remains one of the most difficult human diseases to overcome because of its complexity and diversity. Signal transducers and transcriptional activators 3 (STAT3) protein has been found to be overexpressed in a wide range of cancer types. Hyperactivation of STAT3 is particularly associated with low survival in cancer patients.
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