Kinga Kamieniarz-Gdula

University of Oxford | OX · Sir William Dunn School of Pathology

Usage of alternative mRNA 3′ ends has profound functional consequences, particularly in the nervous system. In this issue of Neuron, LaForce et al. (2022) dissect the effect of CLP1 on mRNA 3′ end diversity in motor neuron models of neurodegeneration.

The concept of early termination as an important means of transcriptional control has long been established. Even so, its role in metazoan gene expression is underappreciated. Recent technological advances provide novel insights into premature transcription termination (PTT). This process is frequent, widespread, and can occur close to the transcri...

The concept of premature termination as an important means of transcriptional control is long established. Even so, its role in metazoan gene expression is underappreciated. Recent technological advances provide novel insights into premature transcription termination (PTT). PTT is very frequent and wide-spread, being either TSS-associated or intrag...

The concept of premature termination as an important means of transcriptional control is long established. Even so, its role in metazoan gene expression is underappreciated. Recent technological advances provide novel insights into premature transcription termination (PTT). PTT is very frequent and wide-spread, being either TSS-associated or intrag...

The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for...

The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for...

Nuclear gene transcription is coordinated with transcript release from the chromatin template and messenger RNA (mRNA) export to the cytoplasm. Here we describe the role of nuclear-localized kinase WNK1 (with no lysine [K] 1) in the mammalian mRNA export pathway even though it was previously established as a critical regulator of ion homeostasis in...

The mechanisms contributing to transcription-associated genomic instability are both complex and incompletely understood. Although R-loops are normal transcriptional intermediates, they are also associated with genomic instability. Here, we show that BRCA1 is recruited to R-loops that form normally over a subset of transcription termination regions...

The formation of R-loops is a natural consequence of the transcription process, caused by invasion of the DNA duplex by nascent transcripts. These structures have been considered rare transcriptional by-products with potentially harmful effects on genome integrity owing to the fragility of the displaced DNA coding strand. However, R-loops may also...

Dicer is a central enzymatic player in RNA-interference pathways that acts to regulate gene expression in nearly all eukaryotes. Although the cytoplasmic function of Dicer is well documented in mammals, its nuclear function remains obscure. Here we show that Dicer is present in both the nucleus and cytoplasm, and its nuclear levels are tightly regu...

Human cells contain five canonical, replication-dependent somatic histone H1 subtypes (H1.1, H1.2, H1.3, H1.4, and H1.5). Although they are key chromatin components, the genomic distribution of the H1 subtypes is still unknown, and their role in chromatin processes has thus far remained elusive. Here, we map the genomic localization of all somatic...

Histone modifications are key regulators of chromatin function. However, little is known to what extent histone modifications can directly impact on chromatin. Here, we address how a modification within the globular domain of histones regulates chromatin function. We demonstrate that H3K122ac can be sufficient to stimulate transcription and that mu...

RNA Polymerase II (Pol II) termination is dependent on RNA processing signals as well as specific terminator elements located downstream of the poly(A) site. One of the two major terminator classes described so far is the Co-Transcriptional Cleavage (CoTC) element. We show that homopolymer A/T tracts within the human β-globin CoTC-mediated terminat...

Histone variants are non-allelic protein isoforms that play key roles in diversifying chromatin structure. The known number of such variants has greatly increased in recent years, but the lack of naming conventions for them has led to a variety of naming styles, multiple synonyms and misleading homographs that obscure variant relationships and comp...

The linker histone H1 is a key player in chromatin organization, yet our understanding of the regulation of H1 functions by post-translational modifications is very limited. We provide here the first functional characterization of H1 acetylation. We show that H1.4K34 acetylation (H1.4K34ac) is mediated by GCN5 and is preferentially enriched at prom...

Supplementary materials and methods.

Figure S1 - Identification of protein arginine methyltransferase (PRMT)1 as a histone H2A methyltransferase, using nanoscale liquid chromatography and mass spectrometry (MS). The two fractions (numbers 4 and 6) from the heparin column (Figure 1B) containing methyltransferase activity towards histone H2A 4-129 were analysed by MS as described (see A...

Figure S3 - Characterisation of the novel H2AR29me2a antibody. (A) The indicated amounts of unmodified H2AR29 peptide, monomethylated H2AR29 peptide, asymmetrically dimethylated H2AR29 peptide (aa 25 to 34 of H2A) and asymmetrically dimethylated H2AR3 peptide (aa 1 to 8) were spotted onto a membrane and probed with the H2AR29me2a antibodies. This a...

Figure S4 - Identification of H2AR29me2 in vivo by mass spectrometry (MS) analysis. (A) Overlay of the collisionally activated dissociation (CAD) tandem MS (MS/MS) spectra (derived from the endogenous H2A, isolated from Raji cells) of the specific tryptic (18 hour digest) peptide 22AGLQFPVGR(me2)29 (black) and the corresponding synthetic peptide (s...

Figure S2 - Purification and immunoprecipitation of the different protein arginine methyltransferases (PRMTs). (A) Immunoprecipitation of Flag-hemagglutinin (HA)-tagged PRMTs from stable cell lines with HA-specific antibodies. Western blots with HA antibodies are shown. Control for Figure 2A (B) Immunofluorescence with Flag-specific antibody of sta...

Table S1: Primers used in this study.

Covalent histone modifications are central to all DNA-dependent processes. Modifications of histones H3 and H4 are becoming well characterised, but knowledge of how H2A modifications regulate chromatin dynamics and gene expression is still very limited. To understand the function of H2A modifications, we performed a systematic analysis of the histo...

Covalent modifications of histones can regulate all DNA-dependent processes. In the last few years, it has become more and more evident that histone modifications are key players in the regulation of chromatin states and dynamics as well as in gene expression. Therefore, histone modifications and the enzymatic machineries that set them are crucial...

The aim of the present study was to determine the prevalence of Leptotrichia amnionii in cervical swabs of women and its possible correlation with HPV infection and the stage of cervical cancer. A total of 139 cervical swabs from healthy women with normal cytology, with dysplastic changes and with cervical cancer were tested for the presence of L.a...

In the nucleus of eukaryotic cells, DNA is tightly associated with proteins forming a structure known as chromatin. These protein/DNA associations allow high compaction of the DNA, and e.g., at the same time, ensure its accessibility for the transcription and replication machinery. The building blocks of chromatin are nucleosomes, which consist of...

The linker histone H1 binds to the DNA entering and exiting the nucleosomal core particle and has an important role in establishing and maintaining higher order chromatin structures. H1 forms a complex family of related proteins with distinct species, tissue and developmental specificity. In higher eukaryotes all H1 variants have the same general s...

Via its extracellular N-terminal domain (NTD), the AMPA receptor subunit GluR2 promotes the formation and growth of dendritic spines in cultured hippocampal neurons. Here we show that the first N-terminal 92 amino acids of the extracellular domain are necessary and sufficient for GluR2's spine-promoting activity. Moreover, overexpression of this ex...

We have developed a computer program consisting of 6 subtests assessing the children hand dexterity applicable in the rehabilitation medicine. With its use a normative study on a representative sample of 285 children aged from 7 to 15 (mean age 11.3) was carried out and clinical standards for three age groups (7-9, 9-11, 12-15 years) were proposed....