Biology subjects

Parker, R.

Publications and source records attributed to Parker, R..

4 recordsLinked to original sources

bioRxiv2018

mRNP architecture in translating and stress conditions reveals an ordered pathway of mRNP compaction

Stress granules (SGs) are non-translating mRNP assemblies that form during stress. Herein, we use multiple smFISH probes for specific mRNAs to examine their SG recruitment and spatial organization. We observed that ribosome run-off is required for SG entry with long ORF mRNAs being delayed in SG accumulation, revealing SG transcriptome changes over time. Moreover, mRNAs are ~20X compacted from an expected linear length when translating and compact ~2 fold further in a stepwise manner beginning at the 5 end during ribosome run-off. Surprisingly, the 5 and 3 ends of the examined mRNAs were separated in non-stress conditions, but in non-translating conditions, the ends of AHNAK and DYNC1H1 mRNAs become close, suggesting the closed-loop model of mRNPs preferentially forms on non-translating mRNAs. These results suggest translation inhibition triggers a mRNP reorganization that brings ends closer, which has implications for the regulation of mRNA stability and translation by 3 UTR elements and the poly(A) tail.

molecular biology↗

bioRxiv2018

Imaging of single mRNA translation repression reveals diverse interactions with mRNP granules

During cellular stress mRNAs exit translation and accumulate in stress granules and P-bodies, although the dynamics of these interactions remain unclear. We imaged in real-time single mRNAs, their translational output, and mRNA-granule interactions during stress. We observed single mRNAs interacting with stress granules and P-bodies, with mRNAs moving bidirectionality between them. While translating mRNAs only interact with RNP granules dynamically, non-translating mRNAs can form stable associations that rigidly immobilize the mRNA within the granule. Imaging thousands of individual mRNA-granule interactions showed the probability of stable association increases with both mRNA length and granule size. Therefore, the recruitment of mRNAs to RNP granules involves both highly dynamic and stable interactions, influenced by several parameters, demonstrating a new layer of complexity in mRNA regulation during stress.\n\nOne Sentence SummarymRNAs interact with stress granules and P-bodies in stable and dynamic manners influenced by ribosome association, mRNA length, and granule size.

molecular biology↗

bioRxiv2017

The Anorexia Nervosa Genetics Initiative: Overview and Methods

BackgroundGenetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13000 individuals with AN as well as ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research.\n\nMethodsANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H.\n\nResultsBlood samples and clinical information were collected from 13,364 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable.\n\nConclusionsOur multipronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.gov NCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

genetics↗

bioRxiv2017

Intrinsically disordered regions contribute promiscuous interactions to RNP granule assembly

Eukaryotic cells contain large RNA-protein assemblies referred to as RNP granules, whose assembly is promoted by both traditional protein interactions and intrinsically disordered protein domains. Using RNP granules as an example, we provide evidence for an assembly mechanism of large cellular structures wherein specific protein-protein or protein-RNA interactions act together with promiscuous interactions of intrinsically disordered regions (IDRs). This synergistic assembly mechanism illuminates RNP granule assembly, and explains why many components of RNP granules, and other large dynamic assemblies, contain IDRs linked to specific protein-protein or protein-RNA interaction modules. We suggest assemblies based on combinations of specific interactions and promiscuous IDRs are common features of eukaryotic cells.

biochemistry↗