Biology subjects

Tariq, K.

Publications and source records attributed to Tariq, K..

4 recordsLinked to original sources

bioRxiv2026

IGS38, a lncRNA from the human rDNA intergenic spacer, regulates rRNA transcription by altering rDNA chromatin organisation and activating the transcription machinery

The eukaryotic ribosomal genes are multi-copy genes, transcribed from the rDNA, and approximately one third of them is actively transcribed in differentiated cells. A number of lncRNAs have been identified from the intergenic spacer between the rRNA genes, among those the spacer RNA and PAPAS that are involved silencing of rRNA gene copies by altering the chromatin configuration. Here, we have identified lncRNAs that are transcribed from the human rDNA loci and modulate the loci; IGS38 positively regulates rRNA gene transcription by associating to the 47S rRNA gene promoter and modulating the rRNA promoter accessibility while IGS32as associates with heterochromatin. IGS38 binds to the 47S gene promoter through the RNA pol I factors TAF1C and RRN3 as well as the Williams Syndrome Transcription Factor (WSTF), a component of the B-WICH chromatin remodelling complex. The increased accessibility of the promoter stabilises the architectural protein Upstream Binding Factor (UBF) at the rRNA promoter, thereby facilitating RNA pol I promoter escape. Furthermore, IGS38 knock down displays and increased dsRNA abundance in the cytoplasm with a weak induction of the dsRNA sensor OAS2, typically induced by interferon and viral dsRNA. Overall, the both IGS38 and IGS32as are chromatin associated lncRNAs involved in rDNA chromatin changes, and IGS38 is stimulating, together with WSTF, rRNA gene transcription in human cells. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/722362v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@14d4159org.highwire.dtl.DTLVardef@fd773forg.highwire.dtl.DTLVardef@a0030dorg.highwire.dtl.DTLVardef@1285301_HPS_FORMAT_FIGEXP M_FIG C_FIG IGS stabilises 47S rRNA transcription, disruption of IGS38 expression leads to the release of dsRNA in the cytoplasm and a weak immune activation of OAS2. Created by biorender (https://biorender.com/shortURL)

cell biology↗

bioRxiv2024

Malaria-derived hemozoin alters chromatin remodelling and skews dendritic cell responses to subsequent bacterial infections

Hemozoin (HZ), the malaria pigment, is released together with the with the parasite merozoites during the blood stage of the disease, which is connected with the pro-inflammatory response to induce T-cells and B-cells. Co-infections with bacteria lead to a more severe disease progression and the underlying mechanisms are poorly understood. Here, we investigated the impact of HZ on the early response of monocyte-derived dendritic cells (moDC) to a common bacterial component, LPS. A short-term HZ exposure for two hours did not induce an inflammatory response, but it did alter the transcriptional response to LPS. In moDC co-exposed to HZ and LPS, the induction of HLA-DR and PD-L1 gene expression was reduced and associated with decreased binding of RELA compared to LPS-stimulated cells. These gene promoters recruited the silencing chromatin remodelling complex NuRD upon co-exposure, instead of the PBAF complex at the promoter in LPS-stimulated cells. Further, HZ maintained transcription of C-type lectin receptors associated to an immature DC phenotype, DC-SIGN (CD209) and macrophage mannose receptor (MMR/CD206). Here, activated RELA and IRF3 were recruited in a PBAF and ncBAF dependent manner. Upon LPS co-exposure, NuRD was replacing these complexes to allow for a reduced transcriptional level of these immature markers. The association of chromatin remodelling complexes did not alter the chromatin state at the promoters, which was changed during differentiation to DCs or even at an earlier point. In conclusion, HZ exposure primes specific gene promoters at an early time point, which results in a different transcriptional response and may also lead to a changed immune reaction to bacterial co-infections. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=136 SRC="FIGDIR/small/585548v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@1573c58org.highwire.dtl.DTLVardef@3aeb6forg.highwire.dtl.DTLVardef@36f4bdorg.highwire.dtl.DTLVardef@1fddcd2_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

Seqpac: A New Framework for small RNA analysis in R using Sequence-Based Counts

Small RNA sequencing (sRNA-seq) has become important for studying regulatory mechanisms in many cellular processes. Data analysis remains challenging, mainly because each class of sRNA--such as miRNA, piRNA, tRNA- and rRNA-derived fragments (tRFs/rRFs)--needs special considerations. Analysis therefore involves complex workflows across multiple programming languages, which can produce research bottlenecks and transparency issues. To make analysis of sRNA more accessible and transparent we present seqpac: a tool for advanced group-based analysis of sRNA completely integrated in R. This opens advanced sRNA analysis for Windows users--from adaptor trimming to visualization. Seqpac provides a framework of functions for analyzing a PAC object, which contains 3 standardized tables: sample phenotypic information (P), sequence annotations (A), and a counts table with unique sequences across the experiment (C). By applying a sequence-based counting strategy that maintains the integrity of the fastq sequence, seqpac increases flexibility and transparency compared to other workflows. It also contains an innovative targeting system allowing sequence counts to be summarized and visualized across sample groups and sequence classifications. Reanalyzing published data, we show that seqpacs fastq trimming performs equal to standard software outside R and demonstrate how sequence-based counting detects previously unreported bias. Applying seqpac to new experimental data, we discovered a novel rRF that was down-regulated by RNA pol I inhibition (anticancer treatment), and up-regulated in previously published data from tumor positive patients. Seqpac is available on github (https://github.com/Danis102/seqpac), runs on multiple platforms (Windows/Linux/Mac), and is provided with a step-by-step vignette on how to analyze sRNA-seq data.

bioinformatics↗

bioRxiv2020

A novel isoform of ACE2 is expressed in human nasal and bronchial respiratory epithelia and is upregulated in response to RNA respiratory virus infection

Angiotensin-converting enzyme 2 (ACE2) is the main entry point in the airways for SARS-CoV-2. ACE2 binding to SARS-CoV-2 protein Spike triggers viral fusion with the cell membrane, resulting in viral RNA genome delivery into the host. Despite ACE2s critical role in SARS-CoV-2 infection, an understanding of ACE2 expression, including in response to viral infection, remains unclear. Until now ACE2 was thought to encode five transcripts and one 805 amino acid protein. Here we identify a novel short isoform of ACE2. Short ACE2 is expressed in the airway epithelium, the main site of SARS-CoV-2 infection; it is substantially upregulated in response to interferon stimulation and RV infection, but not in response to SARS-CoV-2 infection, and it shows differential regulation in asthma patients. This short isoform lacks SARS-CoV-2 spike glycoprotein high-affinity binding sites and altogether, our data are consistent with a model where short ACE2 may influence host susceptibility to SARS-CoV-2 infection.

molecular biology↗