Biology subjects

Rebbani, K.

Publications and source records attributed to Rebbani, K..

3 recordsLinked to original sources

bioRxiv2026

Global Regulatory Functions of the Human CCR4-NOT Complex in mRNA Deadenylation and Decay

Shortening of the poly(A) tail initiates mRNA decay, and the human CCR4-NOT is the principal cytoplasmic deadenylase. Although its subunits have been defined, their functions have not been comprehensively evaluated in cells. We depleted each CCR4-NOT subunit and measured transcriptome-wide effects. CCR4-NOT regulated transcripts from thousands of genes, many of which associated with the complex in cells. Distinct groups of transcripts responded according to the modular organization of the complex, while subsets exhibited unique responses to specific subunits. Poly(A) tail analysis revealed that the CNOT7 and CNOT8 deadenylases are the predominant regulators of poly(A) tail length in these cells. CCR4-NOT targets were enriched in regulatory pathways including cell proliferation, apoptosis, stress responses, and cancer-related processes. Bioinformatic analysis identified sequence determinants and candidate recruitment factors associated with CCR4-NOT regulation. The results define the breadth and specificity of CCR4-NOT-mediated mRNA decay and provide a resource for dissecting regulatory mechanisms and biological roles.

biochemistry↗

bioRxiv2023

A paradigm for regulation at the effector interface with RNA-binding proteins

RNA-binding proteins (RBPs) are key regulators of gene expression, but how RBPs convey regulatory instructions to the core effectors of RNA processing is unclear. Here we document the existence and functions of a multivalent RBP-effector interface. We show that the effector interface of a deeply conserved RBP with an essential role in metazoan development, Unkempt, is mediated by a novel type of dual-purpose peptide motifs that can contact two different surfaces of interacting proteins. Unexpectedly, we find that the multivalent contacts do not merely serve effector recruitment but are required for the accuracy of RNA recognition by the recruiting RBP. Systems analyses reveal that multivalent RBP-effector contacts can repurpose the principal activity of an effector for a different function, as we demonstrate for reuse of the central eukaryotic mRNA decay factor CCR4-NOT in translational control. Our study establishes the molecular assembly and functional principles of an RBP-effector interface, with implications for the evolution and function of RBP-operated regulatory networks.

molecular biology↗

bioRxiv2019

ZBTB33 (Kaiso) methylated binding sites are associated with primed heterochromatin

BackgroundZBTB33, also known as Kaiso, is a member of the zinc finger and BTB/POZ family. In contrast to many transcription factors, ZBTB33 has the ability to bind both a sequence-specific consensus and methylated DNA. Although these dual binding preferences enable ZBTB33 to function as an active as well as repressive regulator of gene expression, little is known about the underlining molecular mechanisms.\n\nResultsIn this study, we aimed to investigate the role of ZBTB33 as a methylated DNA binding factor. We took advantage of the latest releases of the ENCODE sequencing datasets, including ZBTB33 ChIP- seq, whole genome bisulfite sequencing (WGBS), histone mark ChIP-seq and sequencing assays determining the chromatin states, to characterize the chromatin landscapes surrounding methylated ZBTB33 binding sites. Interestingly, our integrative analyses demonstrated that the majority of methylated ZBTB33 binding sites were located within condensed chromatin, which are inaccessible to DNase I and Tn5 transposase. Moreover, these sites were carrying a newly revealed histone post-translational modification signature, with significant enrichment of mono-methylation at lysine 4 of histone 3 (H3K4me1) and a complete absence of other active or expected repressive histone marks.\n\nConclusionsOverall, our analyses revealed that ZBTB33 has the unique ability to bind methylated DNA across heterochromatin in a transition state, suggesting a potential role for ZBTB33 in heterochromatin priming.

genomics↗