scholarly journals Regulation of Histone H4 Lys16 Acetylation by Predicted Alternative Secondary Structures in roX Noncoding RNAs

2008 ◽  
Vol 28 (16) ◽  
pp. 4952-4962 ◽  
Author(s):  
Seung-Won Park ◽  
Mitzi I. Kuroda ◽  
Yongkyu Park
Keyword(s):  
Drosophila Melanogaster ◽  
X Chromosome ◽  
Noncoding Rnas ◽  
Loop Structure ◽  
Histone H4 ◽  
Stem Loop ◽  
Functional Conservation ◽  
Stem Loop Structure ◽  
Msl Complex ◽  
H4k16 Acetylation

ABSTRACT Despite differences in size and sequence, the two noncoding roX1 and roX2 RNAs are functionally redundant for dosage compensation of the Drosophila melanogaster male X chromosome. Consistent with functional conservation, we found that roX RNAs of distant Drosophila species could complement D. melanogaster roX mutants despite low homology. Deletion of a conserved predicted stem-loop structure in roX2, containing a short GUb (GUUNUACG box) in its 3′ stem, resulted in a defect in histone H4K16 acetylation on the X chromosome in spite of apparently normal localization of the MSL complex. Two copies of the GUb sequence, newly termed the “roX box,” were functionally redundant in roX2, as mutants in a single roX box had no phenotype, but double mutants showed reduced H4K16 acetylation. Interestingly, mutation of two of three roX boxes in the 3′ end of roX1 RNA also reduced H4K16 acetylation. Finally, fusion of roX1 sequences containing a roX box restored function to a roX2 deletion RNA lacking its cognate roX box. These results support a model in which the functional redundancy between roX1 and roX2 RNAs is based, at least in part, on short GUUNUACG sequences that regulate the activity of the MSL complex.

scholarly journals Functional Redundancy Within roX1, a Noncoding RNA Involved in Dosage Compensation in Drosophila melanogaster

Genetics ◽  
2003 ◽  
Vol 164 (3) ◽  
pp. 1003-1014
Author(s):  
Carsten Stuckenholz ◽  
Victoria H Meller ◽  
Mitzi I Kuroda
Keyword(s):  
Drosophila Melanogaster ◽  
X Chromosome ◽  
Noncoding Rna ◽  
Rna Stability ◽  
Loop Structure ◽  
Stem Loop ◽  
Stem Loop Structure ◽  
Expression Of Genes ◽  
Rna Domains ◽  
Rna Disruption

Abstract Drosophila melanogaster males dosage compensate by twofold upregulation of the expression of genes on their single X chromosome. This process requires at least five proteins and two noncoding RNAs, roX1 and roX2, which paint the male X chromosome. We used a deletion analysis to search for functional RNA domains within roX1, assaying RNA stability, targeting of the MSL proteins to the X, and rescue of male viability in a roX1-  roX2- mutant background. We found that deletion of 10% segments of the RNA did not dramatically reduce function in most cases, suggesting extensive internal redundancy. The 3′ 600 nt of roX1 were most sensitive to mutations, affecting proper localization and 3′ processing of the RNA. Disruption of an inverted repeat predicted to form a stem-loop structure was found partially responsible for the defects observed.

scholarly journals An approach for the identification of microRNA with an application to Anopheles gambiae.

2006 ◽  
Vol 53 (2) ◽  
pp. 303-309 ◽  
Author(s):  
Raghunath Chatterjee ◽  
Keya Chaudhuri
Keyword(s):  
Drosophila Melanogaster ◽  
Anopheles Gambiae ◽  
Rna Folding ◽  
Noncoding Rnas ◽  
Phylogenetic Distance ◽  
Loop Structure ◽  
Stem Loop ◽  
Stem Loop Structure ◽  
Related Organism ◽  
Post Transcriptional Regulation

MicroRNAs (miRNAs) are an abundant class of 20-27 nt long noncoding RNAs, involved in post-transcriptional regulation of genes in eukaryotes. These miRNAs are usually highly conserved between the genomes of related organisms and their pre-miRNA transcript, about 60-120 nt long, forms extended stem-loop structure. Keeping these facts in mind miRsearch is developed which relies on searching the homologues of all known miRNAs of one organism in the genome of a related organism allowing few mismatches depending on the phylogenetic distance between them, followed by assessing for the capability of formation of stem-loop structure. The precursor sequences so obtained were then screened through the RNA folding program MFOLD selecting the cut-off values on the basis of known Drosophila melanogaster pre-miRNAs. With this approach, about 91 probable candidate miRNAs along with pre-miRNAs were identified in Anopheles gambiae using known D. melanogaster miRNAs. Out of these, 41 probable miRNAs have 100% similarity with already known D. melanogaster miRNAs and others were found to be at least 85% similar to the miRNAs of various other organisms.

scholarly journals SAFB2 enables the processing of suboptimal stem-loop structures in clustered primary miRNA transcripts

2019 ◽  
Author(s):  
Katharina Hutter ◽  
Michael Lohmüller ◽  
Almina Jukic ◽  
Felix Eichin ◽  
Seymen Avci ◽  
...  
Keyword(s):  
Noncoding Rnas ◽  
General Mechanism ◽  
List Type ◽  
Loop Structure ◽  
Stem Loop ◽  
Protein Coding ◽  
Mirna Processing ◽  
Small Noncoding Rnas ◽  
Stem Loop Structure ◽  
Attachment Factor

SummaryMicroRNAs (miRNAs) are small noncoding RNAs that post-transcriptionally silence most protein-coding genes in mammals. They are generated from primary transcripts containing single or multiple clustered stem-loop structures that are thought to be recognized and cleaved by the DGCR8/DROSHA Microprocessor complex as independent units. Contrasting this view, we here report an unexpected mode of processing of a bicistronic cluster of the miR-15 family, miR-15a-16-1. We find that the primary miR-15a stem-loop is a poor Microprocessor substrate and is consequently not processed on its own, but that the presence of the neighboring primary miR-16-1 stem-loop on the same transcript can compensate for this deficiency in cis. Using a CRISPR/Cas9 screen, we identify SAFB2 (scaffold attachment factor B2) as an essential co-factor in this miR-16-1-assisted pri-miR-15 cleavage, and describe SAFB2 as a novel accessory protein of DROSHA. Notably, SAFB2-mediated cluster assistance expands to other clustered pri-miRNAs including miR-15b, miR-92a and miR-181b, indicating a general mechanism. Together, our study reveals an unrecognized function of SAFB2 in miRNA processing and suggests a scenario in which SAFB2 enables the binding and processing of suboptimal DGCR8/DROSHA substrates in clustered primary miRNA transcripts.Highlightsthe primary miR-15a stem-loop structure per se is a poor Microprocessor substratecleavage of pri-miR-15a requires the processing of an additional miRNA stem-loop on the same RNAsequential pri-miRNA processing or “cluster assistance” is mediated by SAFB proteinsSAFB2 associates with the Microprocessor

Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs

2018 ◽  
Vol 87 (1) ◽  
pp. 323-350 ◽  
Author(s):  
Maria Samata ◽  
Asifa Akhtar
Keyword(s):  
X Chromosome ◽  
Dosage Compensation ◽  
Transcriptional Activation ◽  
Gene Dosage ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Histone H4 ◽  
Chromosome Conformation ◽  
Msl Complex ◽  
Male Specific

X chromosome regulation represents a prime example of an epigenetic phenomenon where coordinated regulation of a whole chromosome is required. In flies, this is achieved by transcriptional upregulation of X chromosomal genes in males to equalize the gene dosage differences in females. Chromatin-bound proteins and long noncoding RNAs (lncRNAs) constituting a ribonucleoprotein complex known as the male-specific lethal (MSL) complex or the dosage compensation complex mediate this process. MSL complex members decorate the male X chromosome, and their absence leads to male lethality. The male X chromosome is also enriched with histone H4 lysine 16 acetylation (H4K16ac), indicating that the chromatin compaction status of the X chromosome also plays an important role in transcriptional activation. How the X chromosome is specifically targeted and how dosage compensation is mechanistically achieved are central questions for the field. Here, we review recent advances, which reveal a complex interplay among lncRNAs, the chromatin landscape, transcription, and chromosome conformation that fine-tune X chromosome gene expression.

scholarly journals Transcription-Coupled Methylation of Histone H3 at Lysine 36 Regulates Dosage Compensation by Enhancing Recruitment of the MSL Complex in Drosophila melanogaster

2008 ◽  
Vol 28 (10) ◽  
pp. 3401-3409 ◽  
Author(s):  
Oliver Bell ◽  
Thomas Conrad ◽  
Jop Kind ◽  
Christiane Wirbelauer ◽  
Asifa Akhtar ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
X Chromosome ◽  
Dosage Compensation ◽  
Histone H3 ◽  
The Body ◽  
Histone H4 ◽  
Histone H3 Methylation ◽  
Msl Complex ◽  
Male Specific ◽  
Active Genes

ABSTRACT In Drosophila melanogaster, dosage compensation relies on the targeting of the male-specific lethal (MSL) complex to hundreds of sites along the male X chromosome. Transcription-coupled methylation of histone H3 lysine 36 is enriched toward the 3′ end of active genes, similar to the MSL proteins. Here, we have studied the link between histone H3 methylation and MSL complex targeting using RNA interference and chromatin immunoprecipitation. We show that trimethylation of histone H3 at lysine 36 (H3K36me3) relies on the histone methyltransferase Hypb and is localized promoter distal at dosage-compensated genes, similar to active genes on autosomes. However, H3K36me3 has an X-specific function, as reduction specifically decreases acetylation of histone H4 lysine 16 on the male X chromosome. This hypoacetylation is caused by compromised MSL binding and results in a failure to increase expression twofold. Thus, H3K36me3 marks the body of all active genes yet is utilized in a chromosome-specific manner to enhance histone acetylation at sites of dosage compensation.

968: Gelsolin Gene Silencing Involving Unusual Chromatin Structures and a Novel Stem Loop Structure of the Promoter Region in Human Bladder Cancer

2004 ◽  
Vol 171 (4S) ◽  
pp. 256-257
Author(s):  
Kazunori Haga ◽  
Ataru Sazawa ◽  
Toru Harabayashi ◽  
Nobuo Shinohara ◽  
Minoru Nomoto ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Gene Silencing ◽  
Promoter Region ◽  
Loop Structure ◽  
Human Bladder Cancer ◽  
Human Bladder ◽  
Stem Loop ◽  
Stem Loop Structure

Detection and sequence analysis of an imperfect stem-loop structure in cis activating gene element from SV40PolyA

2011 ◽  
Vol 33 (4) ◽  
pp. 337-346
Author(s):  
Hong-Gang WANG ◽  
Huan MA ◽  
Zhu LI ◽  
Bin ZHANG ◽  
Xiang-Yang JING ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Loop Structure ◽  
Stem Loop ◽  
Stem Loop Structure ◽  
In Cis ◽  
Gene Element

scholarly journals Locking up the AS1411 Aptamer with a Flanking Duplex: Towards an Improved Nucleolin-Targeting

2021 ◽  
Vol 14 (2) ◽  
pp. 121
Author(s):  
André Miranda ◽  
Tiago Santos ◽  
Eric Largy ◽  
Carla Cruz
Keyword(s):  
Loop Structure ◽  
Binding Properties ◽  
Stem Loop ◽  
Affinity Ligand ◽  
Stem Loop Structure ◽  
Topology Maintenance ◽  
G Quadruplex ◽  
Dimeric Form ◽  
Biophysical Techniques ◽  
Melting Experiments

We have designed AS1411-N6, a derivative of the nucleolin (NCL)-binding aptamer AS1411, by adding six nucleotides to the 5′-end that are complementary to nucleotides at the 3′-end forcing it into a stem-loop structure. We evaluated by several biophysical techniques if AS1411-N6 can adopt one or more conformations, one of which allows NCL binding. We found a decrease of polymorphism of G-quadruplex (G4)-forming sequences comparing to AS1411 and the G4 formation in presence of K+ promotes the duplex folding. We also studied the binding properties of ligands TMPyP4, PhenDC3, PDS, 360A, and BRACO-19 in terms of stability, binding, topology maintenance of AS1411-N6, and NCL recognition. The melting experiments revealed promising stabilizer effects of PhenDC3, 360A, and TMPyP4, and the affinity calculations showed that 360A is the most prominent affinity ligand for AS1411-N6 and AS1411. The affinity determined between AS1411-N6 and NCL denoting a strong interaction and complex formation was assessed by PAGE in which the electrophoretic profile of AS1411-N6 showed bands of the dimeric form in the presence of the ligands and NCL.

scholarly journals Absence of X-chromosome dosage compensation in the primordial germ cells of Drosophila embryos

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryoma Ota ◽  
Makoto Hayashi ◽  
Shumpei Morita ◽  
Hiroki Miura ◽  
Satoru Kobayashi
Keyword(s):  
X Chromosome ◽  
Germ Cells ◽  
Dosage Compensation ◽  
Sex Chromosome ◽  
Primordial Germ Cells ◽  
Histone H4 ◽  
X Chromosomes ◽  
Essential Components ◽  
Msl Complex ◽  
Male Specific

AbstractDosage compensation is a mechanism that equalizes sex chromosome gene expression between the sexes. In Drosophila, individuals with two X chromosomes (XX) become female, whereas males have one X chromosome (XY). In males, dosage compensation of the X chromosome in the soma is achieved by five proteins and two non-coding RNAs, which assemble into the male-specific lethal (MSL) complex to upregulate X-linked genes twofold. By contrast, it remains unclear whether dosage compensation occurs in the germline. To address this issue, we performed transcriptome analysis of male and female primordial germ cells (PGCs). We found that the expression levels of X-linked genes were approximately twofold higher in female PGCs than in male PGCs. Acetylation of lysine residue 16 on histone H4 (H4K16ac), which is catalyzed by the MSL complex, was undetectable in these cells. In male PGCs, hyperactivation of X-linked genes and H4K16ac were induced by overexpression of the essential components of the MSL complex, which were expressed at very low levels in PGCs. Together, these findings indicate that failure of MSL complex formation results in the absence of X-chromosome dosage compensation in male PGCs.

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