mRNA nuclear export: how mRNA identity features distinguish functional RNAs from junk transcripts

Abstract

The division of the cellular space into nucleoplasm and cytoplasm promotes quality control mechanisms that prevent misprocessed mRNAs and junk RNAs from gaining access to the translational machinery. Here, we explore how properly processed mRNAs are distinguished from both misprocessed mRNAs and junk RNAs by the presence or absence of various ‘identity features’.

The GC-content at the 5’ends of human protein-coding genes is undergoing mutational decay

“…It is known that in human protein-coding genes, GC-content peaks around the transcription start site (TSS) and slopes down into both the upstream intergenic region and downstream into the first exon and even the first intron (Xia et al, 2003; Louie et al, 2003; Zhang et al, 2004; Kalari et al, 2006; Haerty and Ponting, 2015; Zhu et al, 2009; Palazzo and Kang, 2021; Palazzo et al, 2024). We wanted to examine this GC-peak more closely by metagene analysis and compare it to other gene landmarks.…”

“…One of the most striking features of human protein coding genes is the pattern of GC-content present along its length (Palazzo et al, 2024; Palazzo and Kang, 2021). In particular, it has been observed that GC-content is highest at the 5’ end of genes, and that this decreases as one travels downstream and is lowest at the 3’ end of genes (Xia et al, 2003; Louie et al, 2003; Zhang et al, 2004; Kalari et al, 2006; Haerty and Ponting, 2015; Zhu et al, 2009; Palazzo and Kang, 2021; Palazzo et al, 2024). In addition, it has been observed that GC-content is higher in exons than in introns, with it being highest in the first exon and decreasing with every subsequent exon (Palazzo et al, 2024; Zhu et al, 2009).…”

“…In addition, it has been observed that GC-content is higher in exons than in introns, with it being highest in the first exon and decreasing with every subsequent exon (Palazzo et al, 2024; Zhu et al, 2009). A similar pattern has been observed in introns (Palazzo et al, 2024; Zhu et al, 2009).…”

“…First, highly spliced mRNAs tend to have high GC-content at their 5’ ends despite the fact that it is not required for export and does not affect expression levels (Mordstein et al, 2020). Second, GC-content extends for quite some distance upstream from the transcriptional start site beyond the promoter region (Louie et al, 2003; Zhang et al, 2004) and downstream into the first intron (Palazzo et al, 2024; Zhu et al, 2009), which are under little selection. Thus it is likely that GC-content is also shaped by non-adaptive forces.…”