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Post-transcriptional regulation of Ribosome Biogenesis in Larp1-deficient cells

ABSTRACT: Post-transcriptional regulation of Ribosome Biogenesis in Larp1-deficient cells

PROVIDER: PRJNA970347 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24466919_1.fastq.gz	Fastqsanger.gz
	SRR24466920_1.fastq.gz	Fastqsanger.gz
	SRR24466921_1.fastq.gz	Fastqsanger.gz
	SRR24466922_1.fastq.gz	Fastqsanger.gz
	SRR24466923_1.fastq.gz	Fastqsanger.gz

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Post-transcriptional regulation of Ribosome Biogenesis in Larp1-deficient cells

Project description:Ribosome biogenesis is a critical aspect of cell differentiation. Ribosome synthesis has been previously reported to be regulated at the transcriptional and post-transcriptional levels. Poly(A) tail-length processing is a hallmark of post-transcriptional regulation associated with different steps of transcript metabolism. Here we monitor the contribution of the RNA-binding protein Larp1 in shaping the poly(A) tail profile of undifferentiated P19 cells. We found that Larp1 prevents the widespread shortening of poly(A) tails below 30 nucleotides and confers additional protection to transcripts containing a 5' terminal oligopyrimidine (TOP) motif, such as those encoding for ribosomal proteins.

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LARP1 mRNP scaffolds mTORC1 to stimulate translation initiation of an essential class of mRNAs

Project description:The RNA biding protein, LARP1, has been proposed to function downstream of mTORC1 to positively regulate the translation of 5M-bM-^@M-^YTOP mRNAs such as ribosome protein (RP) mRNAs. However, its regulatory roles in mTORC1-mediated translation remain unclear. PAR-CLIP of LARP1 revealed its direct and dynamic interactions with RP mRNAs through pyrimidine-enriched sequences in the 5M-bM-^@M-^YUTR of RP mRNAs when mTOR activity is inhibited. Importantly, this LARP1 is a direct substrate of mTORC1 and S6K1/Akt, and phosphorylated LARP1 scaffolds mTORC1 on translation-competent mRNAs to facilitate 4EBP1 and S6K1 phosphorylation. Ablation of LARP1 causes multiple defects in the processes of translation including abnormal eIF4G1 interaction with RP mRNAs and inefficient RP mRNA elongation thereby reducing ribosome biogenesis and cell proliferation. These observations illustrate that LARP1 functions both an effector and a regulator for local mTORC1 activity, and acts as a molecular switch for ribosome biogenesis by sensing growth factor/nutrient signaling. LARP1-bound RNA regions were sequenced from HEK293T cells under growing or mTOR-inactive conditions. In parallel, mRNA abundance was quantified, in biological duplicate, from HEK293T cells under the same conditions.

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Project description:Ribosome biogenesis is a critical component of cell differentiation. Ribosome synthesis has been previously reported to be highly regulated at the transcriptional level, but less is known about its post-transcriptional regulation. Poly(A) tail length regulation is a hallmark of post-transcriptional regulation associated with transcript stability. Here we monitor poly(A) tail length changes at a transcriptome level during P19 differentiation. We found that poly(A) tail shortening occurs during cell differentiation only for transcript encoding for ribosomal proteins. These findings suggest a strong post-transcriptional regulation of ribosome biogenesis during differentiation.

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