Sequences encoding C2H2 zinc fingers inhibit polyadenylation and mRNA export in human cells

Abstract

The large C2H2-Zinc Finger (C2H2-ZNF) gene family has rapidly expanded in primates through gene duplication. There is consequently considerable sequence homology between family members at both the nucleotide and amino acid level, allowing for coordinated regulation and shared functions. Here we show that multiple C2H2-ZNF mRNAs experience differential polyadenylation resulting in populations with short and long poly(A) tails. Furthermore, a significant proportion of C2H2-ZNF mRNAs are retained in the nucleus. Intriguingly, both short poly(A) tails and nuclear retention can be specified by the repeated elements that encode zinc finger motifs. These Zinc finger Coding Regions (ZCRs) appear to restrict polyadenylation of nascent RNAs and at the same time impede their export. However, the polyadenylation process is not necessary for nuclear retention of ZNF mRNAs. We propose that inefficient polyadenylation and export may allow C2H2-ZNF mRNAs to moonlight as non-coding RNAs or to be stored for later use.

Significance of Hypermethylation of Tumor-Suppressor Genes PTGER4 and ZNF43 at CpG Sites in the Prognosis of Colorectal Cancer

“…The use of KAG-308, which is a PTGER4-selective agonist, reduces the risk of colorectal carcinogenesis by promoting mucosa healing and inhibiting macrophage activation [ 28 ]. ZNF43 is a part of the C2H2-zinc finger (C2H2-ZNF) gene family [ 29 ], which is a C2H2-type ZNF-containing protein family and the largest transcription-regulatory factor family included in the human genome by rapid expansion through gene duplication [ 30 ]. A notable homologous sequence between family members exists both at the level of nucleotides and amino acids and enables the formation of a synchronous pattern and shared functions of gene expression.…”

Çok işlevli Proteinler: Moonlight Proteinler

“…Moonlight kavramı sıklıkla proteinleri belirtmek için kullanılmakla birlikte güncel bir çalışmada çinko parmak (ZnF) motif içeren bir protein ailesi olan Cys2His2 (C2H2)-ZNF'ye ait mRNA'ların da sıra dışı bir özelliği keşfedilmiştir. Bu mRNA'lar üzerindeki çinko parmak motiflerinindeki tekrarlı sekansların, mRNA'nın poliadenilasyon sürecini kısıtladığı ve bundan bağımsız olarak mRNA'nın nükleustan sitozole translokasyonunu inhibe ettiği tespit edilmiştir [17]. Bu durum ihtiyaç halinde kullanılmak üzere bu mRNA'ların depolanabileceğini düşündürmekle birlikte moonlight kavramının kapsamını transkript düzeyine genişletme potansiyelini de taşımaktadır.…”

KRAB Zinc Finger protein Znf684 interacts with Nxf1 to regulate mRNA export

“…Krüppel-associated box (KRAB)-containing zinc finger proteins (KZFPs) comprise roughly half (~350) of the human C2H2-ZnFs. KZFPs are capable of recruiting heterochromatin-inducing KAP1 (TRIM28) and are thought to function as repressors of transposable elements (TEs) during early embryogenesis (15).Although C2H2-ZnFs are generally considered to be DNA-binding transcription factors (13,(16)(17)(18), some of these proteins (e.g. CTCF, YY1 and GTF3a) have also been shown to function as RNA-binding proteins (RBPs) (19,20).…”

“…Although C2H2-ZnFs are generally considered to be DNA-binding transcription factors (13,(16)(17)(18), some of these proteins (e.g. CTCF, YY1 and GTF3a) have also been shown to function as RNA-binding proteins (RBPs) (19,20).…”