Examining the intersection between splicing, nuclear export and small RNA pathways

Nabih, Amena; Sobotka, Julia A.; Wu, Monica Z.; Wedeles, Christopher J.; Claycomb, Julie M.

doi:10.1016/j.bbagen.2017.05.027

Cited by 6 publications

(2 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A growing number of studies have linked splicing and nuclear export activities to small RNA pathways in a variety of organisms, but the detailed molecular mechanisms remain largely uncharacterized (Bayne et al, 2008;Xiong et al, 2013;Ameyar-Zazoua et al, 2012;Zhang et al, 2012;Nabih et al, 2017). Splicing and nuclear export are complex, multi-step processes that engage a large and dynamic repertoire of proteins and non-coding RNAs, including the spliceosome, exon junction complex (EJC), and transcription and export complex (TREX) (Kö hler and Hurt, 2007).…”

Section: Introductionmentioning

confidence: 99%

The Conserved Intron Binding Protein EMB-4 Plays Differential Roles in Germline Small RNA Pathways of C. elegans

Tyc

Nabih

et al. 2017

Developmental Cell

Self Cite

View full text Add to dashboard Cite

Proper regulation of the germline transcriptome is essential for fertility. In C. elegans, germline homeostasis hinges on a complex repertoire of both silencing and activating small RNA pathways, along with RNA processing. However, our understanding of how fundamental RNA processing steps intersect with small RNA machineries in the germline remains limited. Here, we link the conserved intron binding protein, EMB-4/AQR/IBP160, to the CSR-1 and HRDE-1 nuclear 22G-RNA pathways in the C. elegans germline. Loss of emb-4 leads to distinct alterations in CSR-1- versus HRDE-1-associated small RNA and mRNA transcriptomes. Our transcriptome-wide analysis shows that EMB-4 is enriched along pre-mRNAs of nearly 8,000 transcripts. While EMB-4 complexes are enriched for both intronic and exonic sequences of HRDE-1 targets, CSR-1 pathway targets are enriched for intronic, but not exonic, sequences. These data suggest that EMB-4 could contribute to a molecular signature that distinguishes the targets of these two germline small RNA pathways.

show abstract

Section: Introductionmentioning

confidence: 99%

The Conserved Intron Binding Protein EMB-4 Plays Differential Roles in Germline Small RNA Pathways of C. elegans

Tyc

Nabih

et al. 2017

Developmental Cell

Self Cite

View full text Add to dashboard Cite

show abstract

“…This provides a first important cytological hallmark for the endogenous HRDE-1 targets. Nuclear RNA export is coupled with transcription and RNA processing [40]. Aberrant RNAs that fail to be exported are subjected to nuclear RNA degradation.…”

Section: Is Nuclear Accumulation a Sign Of "Foreign"?mentioning

confidence: 99%

The spatial and temporal dynamics of the nuclear RNAi-targeted RNA transcripts inCaenorhabditis elegans

Kalinava

Mendoza

et al. 2018

Preprint

View full text Add to dashboard Cite

Small RNA-guided chromatin silencing, also referred to as nuclear RNAi, plays an essential role in genome surveillance in eukaryotes and provides a unique paradigm to explore the complexity in RNA-mediated chromatin regulation and transgenerational epigenetics. A well-recognized paradox in this research area is that transcription of the target loci is necessary for the initiation and maintenance of the silencing at the same loci. How the two opposing activities (transcriptional activation and repression) are coordinated during animal development is poorly understood. To resolve this gap, we took single-molecule RNA imaging, deep-sequencing, and genetic approaches towards delineating the developmental regulation and subcellular localization of RNA transcripts of two exemplary endogenous germline nuclear RNAi targets in C. elegans, Cer3 and Cer8 LTR retrotransposons.By examining the wild type and a collection of mutant strains, we found that transcription and silencing cycle of Cer3 and Cer8 is tightly coupled with the early embryogenesis and germline mitotic and meiotic cell cycles. Strikingly, Cer3 and Cer8 transcripts are exclusively localized in the nuclei of germ cells in both wild type and germline nuclear RNAi-defective mutant animals. RNA-sequencing analysis found that this nuclear enrichment feature is a general feature for the endogenous targets of the germline nuclear RNAi pathway. In addition, the germline and somatic repressions of Cer3 have different genetic requirement for the three H3K9 histone methyltransferases, MET-2, SET-25, and SET-32, in conjunction with the nuclear Argonaute protein WAGO-9/HRDE-1. These results provide a first comprehensive cellular and developmental characterization of the nuclear RNAi-targeted endogenous targets throughout animal reproductive cycle. Altogether, these results support a model in which (1) both the transcriptional activation and repression steps of the germline nuclear RNAi pathway are tightly coupled with animal development, (2) the endogenous targets exhibit a hallmark of nuclear enrichment of their transcripts, and (3) different heterochromatin enzymes play distinct roles in somatic and germline silencing of the endogenous targets.

show abstract

Biochemistry of Synthetic Biology - Recent Developments

O’Donoghue

Heinemann

2017

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Examining the intersection between splicing, nuclear export and small RNA pathways

Cited by 6 publications

References 101 publications

The Conserved Intron Binding Protein EMB-4 Plays Differential Roles in Germline Small RNA Pathways of C. elegans

The Conserved Intron Binding Protein EMB-4 Plays Differential Roles in Germline Small RNA Pathways of C. elegans

The spatial and temporal dynamics of the nuclear RNAi-targeted RNA transcripts inCaenorhabditis elegans

Biochemistry of Synthetic Biology - Recent Developments

Contact Info

Product

Resources

About