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MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus synthetic construct

PROVIDER: GSE196458 | GEO | 2022/03/31

REPOSITORIES: GEO

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MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position.

Project description:MicroRNAs (miRNAs), in association with Argonaute (AGO) proteins, direct repression by pairing to sites within mRNAs. Compared to pairing preferences of the miRNA seed region (nucleotides 2-8), preferences of the miRNA 3' region are poorly understood, due to the sparsity of measured affinities for the many pairing possibilities. We used RNA bind-n-seq with purified AGO2-miRNA complexes to measure relative affinities of >1000 3'-pairing architectures for each miRNA. In some cases, optimal 3' pairing increased affinity by >500 fold. Some miRNAs had two high-affinity 3'-pairing modes-one of which included additional nucleotides bridging seed and 3' pairing to enable high-affinity pairing to miRNA nucleotide 11. The affinity of binding and the position of optimal pairing both tracked with the occurrence of G or oligo(G/C) nucleotides within the miRNA. These and other results advance understanding of miRNA targeting, providing insight into how optimal 3' pairing is determined for each miRNA.

| S-EPMC8940178 | biostudies-literature

MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position [2]

Project description:MicroRNAs (miRNAs), in association with Argonaute (AGO) proteins, direct repression by pairing to sites within mRNAs. Compared to pairing preferences of the miRNA seed region (nucleotides 2–8), preferences of the miRNA 3′ region are poorly understood, due to the sparsity of measured affinities for the many pairing possibilities. We used RNA bind-n-seq with purified AGO2–miRNA complexes to measure relative affinities of >1,000 3′-pairing architectures for each miRNA. In some cases, optimal 3′ pairing increased affinity by >500-fold. Some miRNAs had two high-affinity 3′-pairing modes—one of which included additional nucleotides bridging seed and 3′ pairing to enable high-affinity pairing to miRNA nucleotide 11. The affinity of binding and the position of optimal pairing both tracked with the occurrence of G or oligo(G/C) nucleotides within the miRNA. These and other results advance understanding of miRNA targeting, providing insight into how optimal 3′ pairing is determined for each miRNA.

2022-03-31 | GSE196457 | GEO

MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position [1]

Project description:MicroRNAs (miRNAs), in association with Argonaute (AGO) proteins, direct repression by pairing to sites within mRNAs. Compared to pairing preferences of the miRNA seed region (nucleotides 2–8), preferences of the miRNA 3′ region are poorly understood, due to the sparsity of measured affinities for the many pairing possibilities. We used RNA bind-n-seq with purified AGO2–miRNA complexes to measure relative affinities of >1,000 3′-pairing architectures for each miRNA. In some cases, optimal 3′ pairing increased affinity by >500-fold. Some miRNAs had two high-affinity 3′-pairing modes—one of which included additional nucleotides bridging seed and 3′ pairing to enable high-affinity pairing to miRNA nucleotide 11. The affinity of binding and the position of optimal pairing both tracked with the occurrence of G or oligo(G/C) nucleotides within the miRNA. These and other results advance understanding of miRNA targeting, providing insight into how optimal 3′ pairing is determined for each miRNA.

2022-03-31 | GSE174715 | GEO

MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position

Project description:MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position

| PRJNA804960 | ENA

MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position [1]

Project description:MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position [1]

| PRJNA731176 | ENA

MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position [2]

Project description:MicroRNA 3'-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position [2]

| PRJNA804962 | ENA

Chx10 consolidates V2a interneuron identity through two distinct gene repression modes

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-07-28 | E-GEOD-83874 | biostudies-arrayexpress

Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes.

Project description:During development, two cell types born from closely related progenitor pools often express identical transcriptional regulators despite their completely distinct characteristics. This phenomenon implies the need for a mechanism that operates to segregate the identities of the two cell types throughout differentiation after initial fate commitment. To understand this mechanism, we investigated the fate specification of spinal V2a interneurons, which share important developmental genes with motor neurons (MNs). We demonstrate that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V2a identity in postmitotic neurons. Chx10 actively promotes V2a fate, downstream of the LIM-homeodomain factor Lhx3, while concomitantly suppressing the MN developmental program by preventing the MN-specific transcription complex from binding and activating MN genes. This dual activity enables Chx10 to effectively separate the V2a and MN pathways. Our study uncovers a widely applicable gene regulatory principle for segregating related cell fates.

| S-EPMC8109239 | biostudies-literature

Chx10 consolidates V2a interneuron identity through two distinct gene repression modes

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-07-28 | GSE83874 | GEO

Chx10 consolidates V2a interneuron identity through two distinct gene repression modes [ChIP-Seq]

Project description:During development, two cell-types born from closely related progenitor pools often express the identical transcriptional regulators despite their completely distinct characteristics. This phenomenon highlights the necessity of the mechanism that operates to segregate the identities of the two cell-types throughout differentiation after initial fate commitment. To understand this mechanism, we investigated the fate specification of spinal V2a interneurons, which share important developmental genes with motor neurons (MNs). Here we demonstrate that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V2a identity in postmitotic neurons. Chx10 actively promotes V2a fate, downstream of the LIM-homeodomain factor Lhx3, while concomitantly suppressing MN developmental program by preventing the MN-specific transcription complex from binding and activating MN genes. This dual activity enables Chx10 to effectively separate V2a and MN pathways. Together, our study uncovers a widely applicable gene regulatory principle for segregating related cell fates. ChIP DNA samples from Chx10-ESC-derived MNs were prepared for sequencing according to the Illumina protocol, and sequenced on the Illumina HiSeq 2000. The peak calling was conducted with MACS software (Zhang et al., 2008). MEME-ChIP Suite (Bailey et al., 2009; Machanick and Bailey, 2011) and TOMTOM algorithm (Gupta et al., 2007) was used for motif analysis.

2016-07-28 | E-GEOD-83872 | biostudies-arrayexpress

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