Enhancer of rudimentary homologue interacts with scaffold attachment factor B at the nuclear matrix to regulate <scp>SR</scp> protein phosphorylation

Drakouli, Sotiria; Lyberopoulou, Aggeliki; Papathanassiou, Maria; Mylonis, Ilias; Georgatsou, Eleni

doi:10.1111/febs.14141

Cited by 22 publications

(45 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Together, these data suggest that ERH, SAFB2, and the N-terminus of DGCR8 act together in the cluster-assisted processing of suboptimal hairpins. It is likely that the large SAFB2 protein may encompass the whole Microprocessor units by interacting with both DROSHA and ERH, because the interaction between ERH and SAFB has been previously reported ( 58 ). SAFB2, however, does not seem to be a stable component of Microprocessor as it was not detected in our isolation experiment (Figure 1 ).…”

Section: Discussionmentioning

confidence: 87%

ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8

Kwon

Jang

Shen

et al. 2020

Nucleic Acids Research

View full text Add to dashboard Cite

The microprocessor complex cleaves the primary transcript of microRNA (pri-miRNA) to initiate miRNA maturation. Microprocessor is known to consist of RNase III DROSHA and dsRNA-binding DGCR8. Here, we identify Enhancer of Rudimentary Homolog (ERH) as a new component of Microprocessor. Through a crystal structure and biochemical experiments, we reveal that ERH uses its hydrophobic groove to bind to a conserved region in the N-terminus of DGCR8, in a 2:2 stoichiometry. Knock-down of ERH or deletion of the DGCR8 N-terminus results in a reduced processing of suboptimal pri-miRNAs in polycistronic miRNA clusters. ERH increases the processing of suboptimal pri-miR-451 in a manner dependent on its neighboring pri-miR-144. Thus, the ERH dimer may mediate ‘cluster assistance’ in which Microprocessor is loaded onto a poor substrate with help from a high-affinity substrate in the same cluster. Our study reveals a role of ERH in the miRNA biogenesis pathway.

show abstract

Section: Discussionmentioning

confidence: 87%

ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8

Kwon

Jang

Shen

et al. 2020

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

“…SRPK1‐mediated phosphorylation of SRSF1 has been shown to regulate alternative splicing of RAC1B [118], which is a hyperactive form of RAC1 [119]. Moreover, ERH appears to regulate SRPK1‐mediated phosphorylation of the lamin B receptor and SR proteins [120]. ERH is also associated with RNA processing complexes.…”

Section: Discussionmentioning

confidence: 99%

Novel FMRP interaction networks linked to cellular stress

et al. 2020

View full text Add to dashboard Cite

Silencing of the fragile X mental retardation 1 (FMR1) gene and consequently lack of synthesis of FMR protein (FMRP) are associated with fragile X syndrome, which is one of the most prevalent inherited intellectual disabilities, with additional roles in increased viral infection, liver disease, and reduced cancer risk. FMRP plays critical roles in chromatin dynamics, RNA binding, mRNA transport, and mRNA translation. However, the underlying molecular mechanisms, including the (sub)cellular FMRP protein networks, remain elusive. Here, we employed affinity pull‐down and quantitative LC‐MS/MS analyses with FMRP. We identified known and novel candidate FMRP‐binding proteins as well as protein complexes. FMRP interacted with 180 proteins, 28 of which interacted with its N terminus. Interaction with the C terminus of FMRP was observed for 102 proteins, and 48 proteins interacted with both termini. This FMRP interactome comprises known FMRP‐binding proteins, including the ribosomal proteins FXR1P, NUFIP2, Caprin‐1, and numerous novel FMRP candidate interacting proteins that localize to different subcellular compartments, including CARF, LARP1, LEO1, NOG2, G3BP1, NONO, NPM1, SKIP, SND1, SQSTM1, and TRIM28. Our data considerably expand the protein and RNA interaction networks of FMRP, which thereby suggest that, in addition to its known functions, FMRP participates in transcription, RNA metabolism, ribonucleoprotein stress granule formation, translation, DNA damage response, chromatin dynamics, cell cycle regulation, ribosome biogenesis, miRNA biogenesis, and mitochondrial organization. Thus, FMRP seems associated with multiple cellular processes both under normal and cell stress conditions in neuronal as well as non‐neuronal cell types, as exemplified by its role in the formation of stress granules.

show abstract

“…In contrast, in model B, the ERH dimer connects two Microprocessors ("inter-complex dimerization of DGCR8 via ERH") ( Figure 6). Because the interaction between ERH and SAFB have been previously reported (55), we may also need to consider a slightly modified model where the large SAFB2 protein encompasses the whole Microprocessor units by interacting with both DROSHA and ERH. Two models may not be mutually exclusive, and both models may work in cells.…”

Section: In Model a Erh Modulates The Interaction Between Two Dgcr8 mentioning

confidence: 99%

ERH as a component of the Microprocessor facilitates the maturation of suboptimal microRNAs

Kwon

Jang

Yang

et al. 2020

Preprint

View full text Add to dashboard Cite

The Microprocessor complex cleaves the primary transcript of microRNA (pri-miRNA) to initiate miRNA maturation. Microprocessor is known to consist of RNase III DROSHA and dsRNA-binding DGCR8. Here we identify Enhancer of Rudimentary Homolog (ERH) as a new component of the Microprocessor. ERH binds to a conserved region in the N-terminus of DGCR8. Knockdown of ERH or deletion of the DGCR8 N-terminus results in a decrease of processing of primary miRNAs with suboptimal hairpin structures that reside in polycistronic miRNA clusters. ERH increases the processing of suboptimal pri-miR-451 in a manner dependent on its neighboring pri-miR-144. Thus, the ERH dimer may mediate "cluster assistance" in which the Microprocessor is loaded onto a poor substrate with help from a high-affinity substrate in the same cluster. Our study reveals a role of ERH in the miRNA pathway.

show abstract

Enhancer of rudimentary homologue interacts with scaffold attachment factor B at the nuclear matrix to regulate SR protein phosphorylation

Cited by 22 publications

References 70 publications

ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8

ERH facilitates microRNA maturation through the interaction with the N-terminus of DGCR8

Novel FMRP interaction networks linked to cellular stress

ERH as a component of the Microprocessor facilitates the maturation of suboptimal microRNAs

Contact Info

Product

Resources

About