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Lin28b augments protein synthesis to control B cell positive selection early in life.

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

ORGANISM(S): Mus musculus

PROVIDER: GSE217788 | GEO | 2022/11/16

REPOSITORIES: GEO

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Lin28b augments protein synthesis to control B cell positive selection early in life [RIP-seq]

Project description:In this study, we identify elevated protein synthesis as a defining characteristic of early life B cell development and a determinant for the qualitative switch in B cell output whereby self-reactive CD5+ B-1 cells becomes censored in postnatal mice This is in part mediated by the heterochronic RNA binding protein LIN28B. To identify Lin28b-dependent, stage specific effects, B cell progenitors at different developmental stages were sorted and analyzed by RNA-seq

2022-11-16 | GSE217787 | GEO

Lin28b augments protein synthesis to control B cell positive selection early in life [RNA-seq]

2022-11-16 | GSE217786 | GEO

Lin28b augments protein synthesis to control B cell positive selection early in life.

Project description:Lin28b augments protein synthesis to control B cell positive selection early in life.

| PRJNA900541 | ENA

Lin28b augments protein synthesis to control B cell positive selection early in life [RIP-seq]

Project description:Lin28b augments protein synthesis to control B cell positive selection early in life [RIP-seq]

| PRJNA900544 | ENA

Lin28b augments protein synthesis to control B cell positive selection early in life [RNA-seq]

Project description:Lin28b augments protein synthesis to control B cell positive selection early in life [RNA-seq]

| PRJNA900545 | ENA

Lin28b controls a neonatal to adult switch in B cell positive selection

Project description:The ability of B-1 cells to become positively selected into the mature B cell pool, despite being weakly self-reactive, has puzzled the field since its initial discovery. Here, we explore changes in B cell positive selection as a function of developmental time by exploiting a link between CD5 surface levels and the natural occurrence of self-reactive B cell receptors (BCRs) in BCR wildtype mice. We show that the heterochronic RNA-binding protein Lin28b potentiates a neonatal mode of B cell selection characterized by enhanced overall positive selection and the developmental progression of CD5+ immature B cells in particular. Importantly, Lin28b achieves this through amplifying the CD19/PI3K/c-Myc positive feedback loop and ectopic Lin28b expression restores both positive selection and mature B cell numbers in CD19–/– adult mice. Thus, the temporally restricted expression of Lin28b alters the rules for B cell selection during ontogeny through modulating tonic signaling. We propose that this neonatal mode of B cell selection represents a cell intrinsic cue to accelerate the de novo establishment of the adaptive immune system and incorporate a layer of natural antibody mediated immunity throughout life.

2019-08-27 | GSE135603 | GEO

SIRT6 suppresses pancreatic cancer through control of Lin28b

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

2016-04-01 | E-GEOD-79505 | biostudies-arrayexpress

Quality control of protein synthesis in the early elongation stage.

Project description:In the early stage of bacterial translation, peptidyl-tRNAs frequently dissociate from the ribosome (pep-tRNA drop-off) and are recycled by peptidyl-tRNA hydrolase. Here, we establish a highly sensitive method for profiling of pep-tRNAs using mass spectrometry, and successfully detect a large number of nascent peptides from pep-tRNAs accumulated in Escherichia coli pthts strain. Based on molecular mass analysis, we found about 20% of the peptides bear single amino-acid substitutions of the N-terminal sequences of E. coli ORFs. Detailed analysis of individual pep-tRNAs and reporter assay revealed that most of the substitutions take place at the C-terminal drop-off site and that the miscoded pep-tRNAs rarely participate in the next round of elongation but dissociate from the ribosome. These findings suggest that pep-tRNA drop-off is an active mechanism by which the ribosome rejects miscoded pep-tRNAs in the early elongation, thereby contributing to quality control of protein synthesis after peptide bond formation.

| S-EPMC10192219 | biostudies-literature

SIRT6 suppresses pancreatic cancer through control of Lin28b

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

2016-04-01 | GSE79505 | GEO

SIRT6 Suppresses Pancreatic Cancer through Control of Lin28b.

Project description:Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD(+)-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1, and IGF2BP3. This epigenetic program defines a distinct subset with a poor prognosis, representing 30%-40% of human PDAC, characterized by reduced SIRT6 expression and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor and uncover the Lin28b pathway as a potential therapeutic target in a molecularly defined PDAC subset. PAPERCLIP.

| S-EPMC4892983 | biostudies-literature

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