Dataset Information

The histone methyltransferase SETD2 couples transcription and splicing by engaging pre-mRNA processing factors through its SHI domain

ABSTRACT: The domains of SETD2, a known histone methyltransferase were investigated for specific interaction partners and function using a number of biochemical assays and affinity purification mass spectrometry. The C-terminal domain, named SETD2C, was identified to interact with hnRNP-L through a previously uncharacterized domain. These findings demonstrate the crosstalk between the transcription and splicing machinery.

INSTRUMENT(S): LTQ

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Michaella Levy

LAB HEAD: Laurence Florens

PROVIDER: PXD022946 | Pride | 2021-02-01

REPOSITORIES: Pride

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Publications

Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing.

Bhattacharya Saikat S Wang Suman S Reddy Divya D Shen Siyuan S Zhang Ying Y Zhang Ning N Li Hua H Washburn Michael P MP Florens Laurence L Shi Yunyu Y Workman Jerry L JL Li Fudong F

Nature communications 20211108 1

The RNA recognition motif (RRM) binds to nucleic acids as well as proteins. More than one such domain is found in the pre-mRNA processing hnRNP proteins. While the mode of RNA recognition by RRMs is known, the molecular basis of their protein interaction remains obscure. Here we describe the mode of interaction between hnRNP L and LL with the methyltransferase SETD2. We demonstrate that for the interaction to occur, a leucine pair within a highly conserved stretch of SETD2 insert their side chai ...[more]

PMID: 34750379

Publication: 1/2

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Project description:Ribosome biogenesis is a highly complex process in eukaryotes, involving temporally and spatially regulated ribosomal protein (r-protein) binding and rRNA remodeling events in the nucleolus, nucleoplasm and cytoplasm. Hundreds of assembly factors (AFs), organized into sequential functional groups, facilitate and guide the maturation process into productive assembly branches in and across different cellular compartments. However, the precise mechanisms by which these AFs function are largely unknown. Here, we use cryo-electron microscopy (cryo-EM), to characterize the structures of yeast nucleoplasmic pre-60S particles affinity-purified using the epitope-tagged AF Nog2. Our data pinpoint the locations and determine the structures of over 20 AFs, which are enriched in two areas, an arc region extending from the central protuberance (CP) to the polypeptide tunnel exit (PTE), and the domain including the internal transcribed spacer 2 (ITS2) that separates 5.8S and 25S rRNAs. These structural data suggest that the arc-located factors might function to chaperone formation of RNA helices found in the active sites of the subunit, including helices from the CP, peptidyl-transferase center (PTC) and intersubunit bridge. In particular, two regulatory GTPases, Nog2 and Nog1, act as hub proteins to interact with multiple, distant AFs and functional rRNA elements, manifesting their critical roles in structural remodeling checkpoints and nuclear export. Moreover, our snapshots of compositionally and structurally different pre-60S intermediates provide essential mechanistic details for three major remodeling events before nuclear export: rotation of the 5S RNP, construction of the active center, and ITS2 removal. Therefore, our structures provide a framework to understand the molecular roles of diverse AFs, and potentially the atomic information therein constitutes a resource to generalize principles governing the elusive functions of nuclear RNA-binding proteins.

Dataset Information

The histone methyltransferase SETD2 couples transcription and splicing by engaging pre-mRNA processing factors through its SHI domain

Publications

Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing.

Similar Datasets

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