Glioblastoma (GBM) is an extremely aggressive and malignant brain tumor that, despite treatment, almost always recurs. This recurrence is potentially driven by quiescent GBM cells, which are in a dormant state, have distinct characteristics, and are thought to be resistant to conventional therapies targeting actively dividing cells. These cells can later re-enter the cell cycle and contribute to tumour recurrence. However, the transcriptional and post-transcriptional machinery involved in the transition from quiescence to the G1 phase in glioblastoma cells is not yet fully understood. Understanding these mechanisms could provide insights into potential therapeutic targets for preventing glioblastoma recurrence. Here, we use a high temporal resolution RNA-seq time course dataset to shed light on transcriptional dynamics and protein domain changes involved in T98G cells transitioning from quiescence to G1. Firstly, by applying Weighted Gene Correlation Network Analysis (WGCNA), we found that glioblastoma quiescence exit is characterized by the presence of separated gene clusters expressed in a sequential temporal manner and associated with different biological processes. Earlier groups were related to processes such as DNA organization, energy metabolism, and immune responses, while later groups were associated with ribosome biogenesis, RNA splicing, protein synthesis, and other processes. Next, we mapped protein domains to isoforms and analyzed the gain or loss of domains between isoform pairs that exhibited 1) opposite temporal expression patterns and 2) a switch in dominance, where one isoform becomes dominant over the other. This approach identified oppositely expressed, dominance-switching isoforms linked to domain loss, which could potentially affect protein function, highlighting the importance of post-transcriptional regulatory mechanisms during quiescence exit. Some of the most representative cases were observed in isoforms from the SPTBN1, MAPKAP1, WDR33, and RBM4 genes, which are known to play crucial roles in regulating cellular processes related to tumour suppression, cancer progression, differentiation, and gene expression.