Co‐transcriptional mRNP formation is coordinated within a molecular mRNP packaging station in S. cerevisiae

Abstract

In eukaryotes, the messenger RNA (mRNA), the blueprint of a protein‐coding gene, is processed and packaged into a messenger ribonucleoprotein particle (mRNP) by mRNA‐binding proteins in the nucleus. The steps of mRNP formation – transcription, processing, packaging, and the orchestrated release of the export‐competent mRNP from the site of transcription for nuclear mRNA export – are tightly coupled to ensure a highly efficient and regulated process. The importance of highly accurate nuclear mRNP formation is illustrated by the fact that mutations in components of this pathway lead to cellular inviability or to severe diseases in metazoans. We hypothesize that efficient mRNP formation is realized by a molecular mRNP packaging station, which is built by several recruitment platforms and coordinates the individual steps of mRNP formation.

Mud2 functions in transcription by recruiting the Prp19 and TREX complexes to transcribed genes

“…Already co-transcriptionally the mRNA is processed: At the 5′ end a cap structure is added, introns are spliced out and—after cleavage at the 3′ end—a poly(A) tail is added. In addition, the mRNA is packaged into a messenger ribonucleoprotein particle (mRNP) by nuclear mRNA binding proteins ( 1–3 ). Only fully processed and packaged mRNPs are exported from the nucleus to the cytoplasm by the conserved mRNA exporter called Mex67-Mtr2 in Saccharomyces cerevisiae and TAP-p15/NXF1-NXT1 in metazoans ( 4–7 ).…”

“…Several nuclear mRNA-binding proteins already bind co-transcriptionally to the mRNA such as the SR-like proteins Nab2 and Npl3 or Tho1 in S. cerevisiae and thus constitute the nuclear mRNP [( 1 ) and references therein]. The recruitment of proteins involved in mRNA processing and mRNP packaging is coordinated with the different phases of transcription by the C-terminal domain (CTD) of Rpb1, the largest subunit of RNAPII ( 1 , 8 , 9 ). The CTD consists of repeats of the heptapeptide sequence YSPTSPS.…”

Quick or quality? How mRNA escapes nuclear quality control during stress

“…Under normal growth conditions a newly transcribed mRNA undergoes several processing steps before it is exported into the cytoplasm. [1][2][3] The major platform for regulation of mRNA maturation is provided by the C-terminal domain (CTD) of Rpb1, the largest catalytically active component of the RNA polymerase II (RNAP II). 4 Changes in the phosphorylation pattern of the CTD's highly conserved YSPTSPS-heptads from the transcription start to the end allow recruitment of proteins at the correct time point.…”

Human THO coordinates transcription termination and subsequent transcript release from the HSP70 locus

“…These different steps in gene expression are interconnected by various trans ‐acting regulatory factors cotranscriptionally loaded to nascent pre‐mRNAs via interactions with the carboxy‐terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAP II). The CTD code, which is composed of different posttranslational modification patterns of the heptapeptide repeats, such as phosphorylation of specific serine residues, primarily determines the timely recruitment of trans ‐acting regulatory factors to active transcriptional machinery during the transcription cycle (Harlen et al, ; Meinel & Sträßer, ; Moore & Proudfoot, ; Müller‐McNicoll & Neugebauer, ; Richard & Manley, ).…”

“…The final stage of the gene expression process, for example, release of mature mRNAs from gene loci, is coupled to CPA, transcriptional termination and subsequent nuclear export (Libri et al, ; Meinel & Sträßer, ; Moore & Proudfoot, ; Richard & Manley, ). Perturbation of these processes in different organisms results in accumulation of mRNAs at or in close proximity to the cognate genes, which are often detected as nuclear transcriptional foci (Custódio et al, ; Hilleren, McCarthy, Rosbash, Parker, & Jensen, ; Jensen, Patricio, McCarthy, & Rosbash, ; Libri et al, ; Qu et al, ; Thomsen, Libri, Boulay, Rosbash, & Jensen, ).…”