A functional connection between the Microprocessor and a variant NEXT

doi:10.1016/j.molcel.2024.10.015

A functional connection between the Microprocessor and a variant NEXT

2024-11-01

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Kristoffer Pors Jakobsen

Torben Heick Jensen *

DOI：10.1016/j.molcel.2024.10.015

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In mammalian cells, primary miRNAs are cleaved at their hairpin structures by the Microprocessor complex, whose core is composed of DROSHA and DGCR8. Here, we show that 5' flanking regions, resulting from Microprocessor cleavage, are targeted by the RNA exosome in mouse embryonic stem cells (mESCs). This is facilitated by a physical link between DGCR8 and the nuclear exosome targeting (NEXT) component ZCCHC8. Surprisingly, however, both biochemical and mutagenesis studies demonstrate that a variant NEXT complex, containing the RNA helicase MTR4 but devoid of the RNA-binding protein RBM7, is the active entity. This Microprocessor-NEXT variant also targets stem-loop-containing RNAs expressed from other genomic regions, such as enhancers. By contrast, Microprocessor does not contribute to the turnover of less structured NEXT substrates. Our results therefore demonstrate that MTR4-ZCCHC8 can link to either RBM7 or DGCR8/DROSHA to target different RNA substrates depending on their structural context.

Keywords:

DIFFERENTIAL EXPRESSION ANALYSIS

CAP-BINDING COMPLEX

PRI-MIRNA

PRIMARY MICRORNAS

RNA DECAY

STRUCTURAL BASIS

MOLECULAR-BASIS

NUCLEAR

DROSHA

TRANSCRIPTS

A functional connection between the Microprocessor and a variant NEXT

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