Biology subjects

Tang, T. T.

Publications and source records attributed to Tang, T. T..

3 recordsLinked to original sources

bioRxiv2025

RNA-binding proteins provide specificity to the PAN2-PAN3 mRNA deadenylation complex

Cytoplasmic shortening of mRNA poly(A) tails represses eukaryotic gene expression by inhibiting efficient translation and committing an mRNA to decay. The CCR4-NOT deadenylase machinery interacts with sequence-specific RNA-binding proteins (RBPs), termed RNA adaptors, to target specific transcripts for deadenylation. In contrast, the PAN2-PAN3 deadenylation complex is thought to be predominantly recruited to mRNAs via interaction with the poly(A) binding protein, raising the question of whether it acts in a transcript-specific manner. Here, using biochemical reconstitution, we show that PAN2-PAN3 can also be recruited to specific RNAs via RNA adaptors, including MEX3, YTHDF and ZFP36 proteins. In cells, we find that a diverse range of RNA adaptors interact with both major deadenylation complexes. Thus, our data suggest that, in addition to CCR4-NOT, PAN2-PAN3 also contributes to the specificity of mRNA degradation and the robustness of post-transcriptional regulation of gene expression.

molecular biology↗

bioRxiv2024

Coordinated regulation by lncRNAs results in tight lncRNA-target couplings

The determination of long non-coding RNA (lncRNA) function is a major challenge in RNA biology with applications to basic, translational, and medical research [1-7]. Our efforts to improve the accuracy of lncRNA-target inference identified lncRNAs that coordinately regulate both the transcriptional and post-transcriptional processing of their targets. Namely, these lncRNAs may regulate the transcription of their target and chaperone the resulting message until its translation, leading to tightly coupled lncRNA and target abundance. Our analysis suggested that hundreds of cancer genes are coordinately and tightly regulated by lncRNAs and that this unexplored regulatory paradigm may propagate the effects of non-coding alterations to effectively dysregulate gene expression programs. As a proof-of-principle we studied the regulation of DICER1 [8, 9]--a cancer gene that controls microRNA biogenesis--by the lncRNA ZFAS1, showing that ZFAS1 activates DICER1 transcription and blocks its post-transcriptional repression to phenomimic and regulate DICER1 and its target microRNAs.

bioinformatics↗

bioRxiv2021

A focal adhesion kinase-YAP signaling axis drives drug tolerant persister cells and residual disease in lung cancer

Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant tumor cells which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.

cancer biology↗