Dataset Information

Ribosome biogenesis mediates the translational increase of non-optimal codon transcripts during IFN stimulation

ABSTRACT: The interferon response is a signaling pathway unique to vertebrates that links the innate and adaptive immune responses. Interferons signal through a cascade of factors including the JAK-STAT pathway to induce the transcription of hundreds of interferon stimulated genes (ISGs). Although the main interferon signal transduction pathways and ISGs have been elucidated, translational regulation of ISG transcripts has not been fully investigated. Prior work demonstrated that ribosomal protein RPL28 negatively regulates a subset of ISGs; however, we find that this effect may be due to a reduction in overall ribosome availability. Multi-omics analysis of RNA-seq and LC-MS/MS data reveal proteins that are translationally up-regulated in IFN-β-stimulated cells depleted of ribosome biogeneis factor BOP1, including an enrichment of ISGs. Analysis of codon usage demonstrates a significant reduction in codon optimality for proteins that are translationally up-regulated during BOP1 knockdown and IFN-β stimulation. Using reporter constructs, we demonstrate that codon non-optimal reporters are translated more that codon-optimized reporters in BOP1-depleted IFN-β cells. We propose that ribosome biogenesis regulates translational fine-tuning of integral protein production to ensure optimal interferon responses.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Brenna Hay

LAB HEAD: Leonard J

PROVIDER: PXD060209 | Pride | 2026-04-30

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20210226_Iceman_10_26-12_A1_1_1152.d.1.dar	Other
	20210226_Iceman_11_26-24_A4_1_1156.d.1.dar	Other
	20210226_Iceman_12_26-8_A3_1_1155.d.1.dar	Other
	20210226_Iceman_14_28-8_A2_1_1154.d.1.dar	Other
	20210226_Iceman_16_28-24_A5_1_1157.d.1.dar	Other

Items per page:

1 - 5 of 89

Similar Datasets

Project description:HIV is able to outpace the innate immune response, including the response mediated by interferon (IFN), to establish a productive infection. However, monocyte derived macrophages (MDMs) may be protected from HIV infection by treatment with type I IFN before virus exposure. The ability of HIV to modulate the type I IFN-mediated innate immune response when it encounters a cell that has already been exposed to IFN was investigated. To investigate the presence of HIV on an established IFN response, MDMs were subjected to four different conditions: (1) IFN-treated only, (2) IFN-treated followed by HIV infection, (3) HIV infected only, and (4) a mock-treated and mock-infected control. Microarray gene expression analysis was performed on a total of 24 samples derived from the 4 conditions assessed at 3 time points (1, 4 and 8 days following treatment/infection) for both IFN-α2 or -ω. Initially, ISGs were identified as those that were upregulated greater than 2-fold by IFN alone (condition 1) at both Days 4 and 8. Then, the IFN-treated condition was compared to the IFN-treated followed by HIV-infection condition in order to identify those ISGs that were downregulated at least 1.5-fold by the presence of HIV at both days. Assuming that it would be counterproductive for HIV infection by itself to induce the expression of ISGs with putative anti-HIV effects, those ISGs that were upregulated greater than 2-fold in the HIV control were removed. Finally, ISGs that passed these filters and were concordant with both IFN-treatments (IFN-α2 and -ω) were identified and corresponded to the following 8 ISGs: AXL receptor tyrosine kinase (AXL), interferon-alpha inducible protein 27 (IFI27), interferon-induced protein 44 (IFI44), interferon-induced protein 44-like (IFI44L), ISG15, OAS1, OAS3 and XIAP associated factor 1 (XAF1). It should be noted that the IFN-α2 and -ω microarray experiments were performed in different batches but batch effects were not corrected since genes were identified by the filtering approach just described within each batch.

Dataset Information

Ribosome biogenesis mediates the translational increase of non-optimal codon transcripts during IFN stimulation

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets