Regulation of nucleolus assembly by non-coding RNA polymerase II transcripts

Caudron-Herger, Maïwen; Pankert, Teresa; Rippe, Karsten

doi:10.1080/19491034.2016.1190890

Cited by 31 publications

(24 citation statements)

References 79 publications

(97 reference statements)

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“…However, it is unclear if recognition of m 6 A-circRNAs by YTHDF2 plays a direct role. One potential model is that m 6 A-circRNAs and m 6 A-mRNAs encoded by the same exons are bundled as part of a chromatin-associated liquid phase transition leading to a nuclear “liquid droplet” (Caudron-Herger et al, 2016; Marzahn et al, 2016) and continue to be a topologically and organizationally distinct information packets. Whereas m 6 A-circRNAs arising from non-methylated exons of mRNAs may not be bundled with mRNAs or are contained in other bundles.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

et al. 2017

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Summary N6-methyladenosine (m6A) is the most abundant internal modification of mRNAs and is implicated in all aspects of post-transcriptional RNA metabolism. However, little is known about m6A modifications to circular (circ) RNAs. We developed a computational pipeline (AutoCirc) that together with depletion of ribosomal RNA and m6A immunoprecipitation defined thousands of m6A-circRNAs, with cell-type-specific expression. The presence of m6A-circRNAs is corroborated by interaction between circRNAs and YTHDF1/YTHDF2, proteins that read m6A sites in mRNAs, and by reduced m6A levels upon depletion of METTL3, the m6A writer. Despite sharing m6A readers and writers, m6A-circRNAs are frequently derived from exons that are not methylated in mRNAs, while mRNAs that are methylated on the same exons that compose m6A-circRNAs exhibit less stability, in a process regulated by YTHDF2. These results expand our understanding of the breadth of m6A modifications and uncover regulation of circRNAs through m6A modification.

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Section: Discussionmentioning

confidence: 99%

Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

et al. 2017

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“…However, the energy dependence might arise from the constant export of nucleolar RNAs into the cytosol, which have to be actively replenished to keep their steady state concentration above the level required for LLPS. Furthermore, cell-cycle-dependent changes in RNA binding properties and posttranslational modifications of nucleolar proteins might change the respective phase equilibria and thereby actively regulate the (dis)assembly of the nucleolus (72).…”

Section: Regulation Of Chromatin Body Formation By Active Processesmentioning

confidence: 99%

Formation of Chromatin Subcompartments by Phase Separation

Erdel

Rippe

2018

Biophysical Journal

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328

340

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Chromatin is partitioned on multiple length scales into subcompartments that differ from each other with respect to their molecular composition and biological function. It is a key question how these compartments can form even though diffusion constantly mixes the nuclear interior and rapidly balances concentration gradients of soluble nuclear components. Different biophysical concepts are currently used to explain the formation of "chromatin bodies" in a self-organizing manner and without consuming energy. They rationalize how soluble protein factors that are dissolved in the liquid nuclear phase, the nucleoplasm, bind and organize transcriptionally active or silenced chromatin domains. In addition to cooperative binding of proteins to a preformed chromatin structure, two different mechanisms for the formation of phase-separated chromatin subcompartments have been proposed. One is based on bridging proteins that cross-link polymer segments with particular properties. Bridging can induce a collapse of the nucleosome chain and associated factors into an ordered globular phase. The other mechanism is based on multivalent interactions among soluble molecules that bind to chromatin. These interactions can induce liquid-liquid phase separation, which drives the assembly of liquid-like nuclear bodies around the respective binding sites on chromatin. Both phase separation mechanisms can explain that chromatin bodies are dynamic spherical structures, which can coalesce and are in constant and rapid exchange with the surrounding nucleoplasm. However, they make distinct predictions about how the size, density, and stability of chromatin bodies depends on the concentration and interaction behavior of the molecules involved. Here, we compare the different biophysical mechanisms for the assembly of chromatin bodies and discuss experimental strategies to distinguish them from each other. Furthermore, we outline the implications for the establishment and memory of functional chromatin state patterns.

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“…They are all found connected to human DNA in disease chromosomes; multiple microbial sequences from different laboratories are all homologous to the same Alu sequence. Alu element-containing RNA polymerase II transcripts (AluRNAs) determine nucleolar structure and rRNA synthesis and may regulate nucleolar assembly as the cell cycle progresses and as the cell adapts to external signals 46 . HIV-1 integration occurs with some preference near or within Alu repeats 47 .…”

Section: Discussionmentioning

confidence: 99%

Parental infections disrupt clustered genes encoding related functions required for nervous system development in newborns

Friedenson¹

2018

Preprint

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The purpose of this study was to understand the role of infection in the origin of chromosomal anomalies linked to neurodevelopmental disorders. In children with disorders in the development of their nervous systems, chromosome anomalies known to cause these disorders were compared to viruses and bacteria including known teratogens. Results support the explanation that parental infections disrupt elaborate multi-system gene coordination needed for neurodevelopment. Genes essential for neurons, lymphatic drainage, immunity, circulation, angiogenesis, cell barriers, structure, and chromatin activity were all found close together in polyfunctional clusters that were deleted in neurodevelopmental disorders. These deletions account for immune, circulatory, and structural deficits that accompany neurologic deficits. In deleted gene clusters, specific and repetitive human DNA matched infections and passed rigorous artifact tests. In some patients, epigenetic driver mutations were found and may be functionally equivalent to deleting a cluster or changing topologic chromatin interactions because they change access to large chromosome segments. In three families, deleted DNA sequences were associated with intellectual deficits and were not included in any database of genomic variants. These sequences were thousands of bp and unequivocally matched foreign DNAs. Analogous homologies were also found in chromosome anomalies of a recurrent neurodevelopmental disorder. Viral and bacterial DNAs that match repetitive or specific human DNA segments are thus proposed to interfere with highly active break repair during meiosis; sometimes delete polyfunctional clusters, and disable epigenetic drivers. Mis-repaired gametes produce zygotes containing rare chromosome anomalies which cause neurologic disorders and accompanying nonneurologic signs. Neurodevelopmental disorders may be examples of assault on the human genome by foreign DNA with some infections more likely tolerated because they resemble human DNA segments. Further tests of this model await new technology.

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Regulation of nucleolus assembly by non-coding RNA polymerase II transcripts

Cited by 31 publications

References 79 publications

Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

Genome-Wide Maps of m6A circRNAs Identify Widespread and Cell-Type-Specific Methylation Patterns that Are Distinct from mRNAs

Formation of Chromatin Subcompartments by Phase Separation

Parental infections disrupt clustered genes encoding related functions required for nervous system development in newborns

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