hnRNP I regulates neonatal immune adaptation and prevents colitis and colorectal cancer

Jin, Zhigang; Liang, Feng; Yang, Jing; Mei, Wenyan

doi:10.1371/journal.pgen.1006672

Cited by 19 publications

(13 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A key advantage of the above-described approach is that by ablating the vRNAprotein interaction site the biological impact of the host-pathogen interaction may be assessed in an unperturbed host system. This enables the characterization of these interactions in wild-type murine models of viral infection, which has been elusive due to the essential nature of many RNA-binding proteins (66)(67)(68)(69)(70). It will be particularly interesting to assess the impact, i.e., what consequences disruption of the hnRNP-vRNA interactions have for viral pathology.…”

Section: Discussionmentioning

confidence: 99%

“…As such, altering the host environment by RNAi would have unintended, and confounding, effects on viral infection. Further supporting this notion is the fact that efforts at developing individual hnRNP knockout animal models have often resulted in severe phenotypes with limited survival (66)(67)(68)(69)(70). Second, many hnRNP proteins are highly abundant in the host cell.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Identification and Characterization of Sindbis Virus RNA-Host Protein Interactions

LaPointe

Gebhart

Meller

et al. 2018

J Virol

View full text Add to dashboard Cite

Arthropod-borne viruses, such as the members of genus , are a significant concern to global public health. As obligate intracellular pathogens, RNA viruses must interact with the host cell machinery to establish, and complete, their viral lifecycles. Despite considerable efforts to define the host/pathogen interactions essential for alphaviral replication, an unbiased and inclusive assessment of alphaviral RNA:protein interactions has not been undertaken. Moreover, the biological and molecular importance of these interactions, in the full context of their molecular function as RNA-binding proteins, has not been fully realized. The data presented here introduces a robust viral RNA:protein discovery method to elucidate the Sindbis virus (SINV) RNA:Protein host interface. Cross-Link Assisted mRNP Purification (CLAMP) assessment reveals an extensive array of host/pathogen interactions centered on the viral RNAs (vRNAs). After prioritization of the host proteins associated with the vRNAs, we identified the site of Protein:vRNA interaction via a CLIP-seq approach and assessed the consequences of the RNA:protein binding event of hnRNP K, hnRNP I, and hnRNP M in regards to viral infection. Herein we demonstrate that mutation of the prioritized hnRNP:vRNA interaction sites effectively disrupted the hnRNP:vRNA interaction. Correlating with disrupted hnRNP:vRNA binding, SINV growth kinetics were reduced relative to wild type parental viral infections in a vertebrate and invertebrate tissue culture models of infection. The molecular mechanism leading to reduced viral growth kinetics were found to be dysregulated structural gene expression. Collectively, this study further defines the scope and importance of the alphavirus host/pathogen vRNA:protein interactions. Members of the genus Alphavirus are widely recognized for their potential to cause severe disease. Despite this recognition, there are no antiviral therapeutics, or safe and effective vaccines, currently available to treat alphaviral infection. Alphaviruses utilize the host cell machinery to efficiently establish and complete their viral lifecycle. However, the extent, and importance, of host/pathogen RNA:protein interactions is woefully under characterized. The efforts detailed in this study fulfill this critical gap; and the significance of this research is three-fold. First, the data presented here fundamentally expands the scope and understanding of alphavirus host/pathogen interactions. Secondly, this study identifies the site of interactions for several prioritized interactions and defines the contribution of the RNA:protein interaction at the molecular level. Finally, these studies build a strategy by which the importance of given host/pathogen interactions may be assessed, in the future, using a mouse model of infection.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of Sindbis Virus RNA-Host Protein Interactions

LaPointe

Gebhart

Meller

et al. 2018

J Virol

View full text Add to dashboard Cite

show abstract

“…In particular, 12 of the 31 identified genes have been reported in the literatures to be related to colon cancer recurrence [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], which can be regarded as validation to our prediction results for these 12 genes. For the other 19 genes identified by us, we cannot exclude the possibility that some of them are due to false positive prediction.…”

Section: Discussionmentioning

confidence: 54%

Exploration of immunogene in colon cancer recurrence

Sun¹,

Yao²,

Yuan³

et al. 2018

Oncotarget

View full text Add to dashboard Cite

Colon adenocarcinoma is the third most common cancer with high risk of recurrence and deteriorative consequences. Given the importance of immune genes in tumor regulation and cancer immunotherapy, there is a need to comprehensively profile the immunoregulatory genes from multiple types of colon cancer patient genomic data for discovering important associations and potential therapeutic targets of colon cancer recurrence. We used publicly available colon tumor tissue genomic data from The Cancer Genome Atlas database and immune genes data from innateDB database in this study. We derived the immune genes profiles by exploring multiple genomic profiles (gene expression, clinical and somatic mutation) in colon cancer. Some of the synthetic lethal genes we identified, such as CASP14, MS4A6E, KIR2DL1, KIR3DL1, KIR2DL3, CCL1, IL36B, FOXO3, POU2F1, SMAD3, HOXA9, PACS1, PROM1, DIDO1, SRC, CBFA2T2, NCOA6, PGAM1 and PROC, have been suggested to be potential targets correlated with immune genes for colon cancer recurrence treatment. Moreover, TLR2 could be promisingly new early stage indicator for colon adenocarcinoma recurrence. This is a systematic study that combines three different types of genomic data to molecularly characterize colon cancer and aims to identify potential targets for colon adenocarcinoma therapy. Meanwhile, the integrative analysis of immune genes for colon cancer could assist in identifying potential new symbols for colon adenocarcinoma recurrence.

show abstract

“…Gastric tissue samples from WT and Myd88 −/− control and H. felis -infected mice were incubated with specific antibodies overnight (Supplementary Table 2) after antigen retrieval in a pressure cooker using 0.01 M sodium citrate. These antibodies have been previously validated by our group and others 36–38 . After incubation with HRP-conjugated secondary antibodies, sections were developed using SignalStain DAB substrate (Cell Signaling) following manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

Increased LIGHT expression and activation of non-canonical NF-κB are observed in gastric lesions of MyD88-deficient mice upon Helicobacter felis infection

Mejías-Luque

Lozano-Pope

Wanisch

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Helicobacter pylori infection induces a number of pro-inflammatory signaling pathways contributing to gastric inflammation and carcinogenesis. Among those, NF-κB signaling plays a pivotal role during infection and malignant transformation of the gastric epithelium. However, deficiency of the adaptor molecule myeloid differentiation primary response 88 (MyD88), which signals through NF-κB, led to an accelerated development of gastric pathology upon H. felis infection, but the mechanisms leading to this phenotype remained elusive. Non-canonical NF-κB signaling was shown to aggravate H. pylori -induced gastric inflammation via activation of the lymphotoxin β receptor (LTβR). In the present study, we explored whether the exacerbated pathology observed in MyD88-deficient ( Myd88 −/− ) mice was associated with aberrant activation of non-canonical NF-κB. Our results indicate that, in the absence of MyD88, H. felis infection enhances the activation of non-canonical NF-κB that is associated with increase in Cxcl9 and Icam1 gene expression and CD3 + lymphocyte recruitment. In addition, activation of signal transducer and activator of transcription 3 (STAT3) signaling was higher in Myd88 −/− compared to wild type (WT) mice, indicating a link between MyD88 deficiency and STAT3 activation in response to H. felis infection. Thereby, MyD88 deficiency results in accelerated and aggravated gastric pathology induced by Helicobacter through activation of non-canonical NF-κB.

show abstract

hnRNP I regulates neonatal immune adaptation and prevents colitis and colorectal cancer

Cited by 19 publications

References 49 publications

Identification and Characterization of Sindbis Virus RNA-Host Protein Interactions

Identification and Characterization of Sindbis Virus RNA-Host Protein Interactions

Exploration of immunogene in colon cancer recurrence

Increased LIGHT expression and activation of non-canonical NF-κB are observed in gastric lesions of MyD88-deficient mice upon Helicobacter felis infection

Contact Info

Product

Resources

About