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Reposted by Vytaute Boreikaite

Plaschka lab @plaschkalab.bsky.social · 08/10/2026

After excising an intron, the spliceosome gets trapped on the branched intron-lariat RNA. How are such dead-end spliceosomes terminated? Our latest paper led by @vytaute.bsky.social investigates the mechanism of spliceosome termination www.nature.com/articles/s41... (1/6)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

This work has been a massive team effort! I’m very grateful to all authors from @plaschkalab.bsky.social, our collaborators in @ameressl.bsky.social, @luijsterburglab.bsky.social and @romangp.bsky.social labs and for the generous funding from EMBO and HFSP. (11/11)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

To sum up, our work reveals how multiple RNA helicases and associated factors gradually unravel the RNA-protein network of the spliceosome after both successful and failed splicing events, sustaining accurate and efficient pre-mRNA processing. (10/11)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

Many of the same factors are implicated in terminating aberrant yeast spliceosomes that fail to splice. We show that such faulty spliceosomes also occur in human cells, suggesting shared but distinct mechanisms to terminate spliceosomes both after successful splicing and in quality control. (9/11)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

How is the DIS finally disassembled? We propose that the 3rd terminating RNA helicase DHX35, assisted by its cofactors GPATCH1 and WDR83, translocates on the U6 snRNA, ejecting the debranched intron for decay and facilitating spliceosome disassembly for recycling. (8/11)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

Surprisingly, we resolved a new spliceosome state with an active site that is almost fully unravelled! Biochemical assays showed that this state results from ILS remodelling. Using RNA-seq, we demonstrated that this untangled spliceosome is bound to debranched introns. Hence, we call it DIS. (7/11)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

Such remodelling may expose the intron-lariat branch point for debranching. Indeed, biochemical and in-cell experiments show that the debranching enzyme DBR1 is tethered to the ILS by the termination factor C19L1, facilitating intron-lariat debranching on the spliceosome. (6/11)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

The ILS-AQR bound to the newly identified termination factor YJU2B revealed how DHX15 and another RNA helicase AQR pull on two different RNAs to begin untangling the spliceosome. This leads to the extraction of the intron-lariat branch point from the dense RNA network of the spliceosome. (5/11)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

Using AlphaFold screens, we identified a set of novel termination factors, including 2 RNA helicases. We then purified the spliceosomes associated with these factors natively from human cells and determined structures of 2 new sequential termination intermediates: (4/11)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

From our previous work, we knew how the intron-lariat spliceosome is recognised and how its remodelling is initiated by the RNA helicase DHX15. www.nature.com/articles/s41... However, the intron-lariat spliceosome turns out not to be the end of the story! (3/11)

nature.com

Mechanism for the initiation of spliceosome disassembly - Nature

Cryo-electron microscopy structures of human and nematode spliceosomes show that the disassembly of this complex is initiated by the licensing of the disassembly helicase to act on the catal...

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

Splicing is a critical event in gene expression. After releasing a spliced mRNA, the spliceosome remains stuck in an unproductive complex trapped on the branched intron-lariat RNA. How are such dead-end spliceosomes disassembled and how are the intron-lariats debranched and released? (2/11)

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Vytaute Boreikaite @vytaute.bsky.social · 08/10/2026

I’m very excited to share my postdoc work in the @plaschkalab.bsky.social, where we investigated the very final act of splicing – spliceosome termination, revealing the stepwise dismantling of the spent spliceosome www.nature.com/articles/s41... (1/11)

nature.com

Mechanism of spliceosome termination - Nature

A coordinated sequence of RNA helicases and associated factors dismantles normal and defective spliceosome complexes to enable intron degradation and ensure accurate gene expression.

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