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Human spliceosome components Smu1 and RED regulate alternative splicing. Here the authors show that Smu1 and RED are also required for constitutive splicing of short introns.

The cryo-EM structure of the splicing intermediate known as the C* complex from human.

Aquarius is an RNA helicase associated with spliceosomes. Lührmann, Pena and colleagues now provide structural insights into how Aquarius is recruited to the spliceosome, revealing a new spliceosomal building block that aids in Aquarius positioning.

Splicing is carried out within a large structure, the spliceosome, containing many RNAs and proteins. In this paper, two intermediary complexes of the splicing reaction have been purified. The differences in these complexes provide a significant advancement in understanding of the composition of the catalytic core.

Cryo-electron microscopy structures of cross-exon pre-B and B-like complexes contribute new insights into the molecular mechanisms that mediate the switch from a cross-exon to a cross-intron organized spliceosome.

The cryo-electron microscopy structure of a newly identified, early spliceosomal complex reveals the mechanism by which the RNA helicase Prp5 enhances the fidelity of the excision of introns from precursor mRNAs.

The cryo-EM structure of human U2 small nuclear ribonucleoprotein (snRNP) offers insights into what rearrangements are required for this snRNP to be stably incorporated into the spliceosome, and the role that the DEAD-box ATPase PRP5 may have in these rearrangements.

PRPF8 is a hotspot for mutations causing retinitis pigmentosa-type 13. Here the authors generated PRPF8 patient-specific retinal cells, demonstrating an important role for this splicing factor in spliceosome kinetics and 5’ splice site selection.

Reversible phosphorylation plays a key role in splicing. Phosphorylation of two splicing components, PRP6 and PRP31, is now shown to be mediated by PRP4. This activity is involved in promoting the stable association of the triple-snRNP to form B complexes, indicating how this kinase promotes building of a stable, functional spliceosome.

The tri-snRNP is the largest preassembled unit of the spliceosome, and its components are key to the splicing reaction. The overall structure and conformations of the yeast tri-snRNP are now analyzed by EM, and the general positions of some of its major protein components mapped.

It is unclear where in the nucleus splicing takes place and how much occurs post-transcriptionally. Using antibodies raised against a phosphorylated splicing factor, Girardet al. show that the majority of splicing occurs co-transcriptionally and that post-transcriptional splicing occurs in nuclear speckles.

Pre-mRNA splicing is catalyzed by the spliceosome in a two-step reaction. Both catalytic steps have now been reconstituted using purified, defined components. This system identifies a role for Cwc25 in the first step of splicing and allows future detailed mechanistic analyses of splicing.

The assembly of the splicesome involves several distinct stages that require the sequential action of DExD/H-box RNA helicases. Here, the authors uncover a new intermediate, the pre-B complex, that accumulates in the presence of an inactive form of the DEAD-box protein Prp28.

So far only a few compounds have been reported as splicing modulators. Here, the authors combine high-throughput screening, chemical synthesis, NMR, X-ray crystallography with functional studies and develop phenothiazines as inhibitors for the U2AF Homology Motif (UHM) domains of proteins that regulate splicing and show that they inhibit early spliceosome assembly on pre-mRNA substrates in vitro.

Mutations in pre-mRNA processing factors cause autosomal dominant retinitis pigmentosa. Here the authors provide insights into the pathophysiological mechanisms underlying non-syndromic retinal disease caused by heterozygous mutations in genes encoding ubiquitously expressed splicing factors.

The function of many non-membrane bound aggregates (Cajal bodies, P-bodies, stress granules, etc.) is poorly understood. Now studies in zebrafish embryos show that coilin promotes spliceosomal small nuclear ribonucleoproteins (snRNPs) assembly, most likely by concentrating snRNP components in Cajal bodies and to overcome a rate-limiting step(s) in assembly.

A solution NMR structure of the pre-mRNA retention and splicing (RES) core complex from budding yeast now reveals how the trimer stabilizes the RRM of its Snu17 subunit to promote pre-mRNA interactions within the spliceosome.

In neurotransmission, synaptic vesicles fuse with the membrane of nerve cells to release neurotransmitter content into the synaptic cleft. This process requires the assembly of several members of the SNARE protein family. Here, the X-ray structure of a neuronal SNARE complex is solved, providing insight into how these proteins assemble.