The pioneer translation initiation complex is functionally distinct from but structurally overlaps with the steady-state translation initiation complex.
In mammalian cells, the pioneer translation initiation complex structurally overlaps with the steady-state translation initiation complex but is functionally distinct. The pioneer translation initiation complex supports the pioneer round of translation. This complex is the primary target of nonsense-mediated mRNA decay (NMD), which is a quality-control pathway (also called an mRNA-surveillance pathway). In contrast, the steady-state translation initiation complex supports the bulk of cellular protein synthesis and is the primary target of pathways that conditionally regulate gene expression.
Models of Nonsense-Mediated mRNA Decay (NMD) and Staufen1(STAU1)-mediated mRNA decay (SMD).
Half of the research in my lab focuses on NMD, which likely evolved to safeguard cells from potentially deleterious proteins produced as a consequence of routine mistakes in gene expression. In mammalian cells, these mistakes include inaccuracies in transcription initiation or pre-mRNA splicing, and ineffective somatic DNA rearrangements of the type that characterize the immunoglobulin and T-cell receptor genes. These mistakes often result in mRNAs having reading frames upstream of the usual reading frame, frameshift mutations that generate nonsense codons, or nonsense mutations. NMD also down-regulates a number of naturally occurring transcripts, including some selenoprotein mRNAs and alternatively spliced RNAs.
The other half of our research focuses on a mechanistically related pathway called Staufen1(STAU1)-mediated mRNA decay (SMD). SMD degrades mRNAs that harbor a binding site for the double-stranded RNA-binding protein STAU1 in their 3'-untranslated regions (3'UTRs). Remarkably, depending on the particular mRNA, STAU1-binding sites (SBSs) can be formed by either intramolecular base-pairing within a 3'UTR or by intermolecular base-pairing between an mRNA 3'UTR and a long non-coding RNA (lnchRNAs) as a means to conditionally regulate gene expression. Like microRNAs, more than one lncRNA can target a single mRNA, and a single lncRNA can target more than one mRNA.
