The interaction between mRNA and ribosomal RNA (rRNA) transcription in cancer remains unclear. RNAP I and II possess a common N-terminal tail (NTT), RNA polymerase subunit RPB6, which interacts with P62 of transcription factor (TF) IIH, and is a common target for the link between mRNA and rRNA transcription. The mRNAs and rRNAs affected by FUBP1-interacting repressor (FIR) were assessed via RNA sequencing and qRT-PCR analysis. An FIR, a c-myc transcriptional repressor, and its splicing form FIRΔexon2 were examined to interact with P62. Protein interaction was investigated via isothermal titration calorimetry measurements. FIR was found to contain a highly conserved region homologous to RPB6 that interacts with P62. FIRΔexon2 competed with FIR for P62 binding and coactivated transcription of mRNAs and rRNAs. Low-molecular-weight chemical compounds that bind to FIR and FIRΔexon2 were screened for cancer treatment. A low-molecular-weight chemical, BK697, which interacts with FIRΔexon2, inhibited tumor cell growth with rRNA suppression. In this study, a novel coactivation pathway for cancer-related mRNA and rRNA transcription through TFIIH/P62 by FIRΔexon2 was proposed. Direct evidence in X-ray crystallography is required in further studies to show the conformational difference between FIR and FIRΔexon2 that affects the P62–RBP6 interaction.

Background: With a growing aging global population, dementia has become an important public health concern. However, few predictive models of cognitive decline include muscle strength as a variable. Objective: This study aimed to assess whether handgrip and knee extensor muscle strengths could be associated with cognitive decline in older Japanese women and to examine the potential contribution of these measurements to established dementia onset prediction models. Methods: A prospective cohort study was conducted involving the data analyzed from 787 community-dwelling aged 65 years and older women, originally from the “Otassha Study.” The baseline handgrip and knee extensor muscle strengths were measured. Cognitive decline was defined as a decrease of three or more points from the baseline score of the Japanese version of the Mini-Mental State Examination. Multivariate analyses were performed adjusting for various potential confounding factors, and interaction effects were explored. The discriminative performances of the extended models were evaluated using receiver operating characteristic (ROC) curve analysis. Results: Notably, lower handgrip and knee extensor muscle strengths were associated with cognitive decline in participants ≥ 75-year-old. Adding handgrip strength to the established models slightly improved the predictive performance, thereof; however, adding knee extensor muscle strength did not. Conclusions: Our study revealed the values of handgrip and knee extensor muscle strengths were associated with cognitive decline among women aged 75 years and older. Incorporating handgrip strength into predictive models enhanced their accuracy, which highlighted the importance of assessing muscle strength to predict cognitive decline in older women.