Transcriptome 3′end organization by PCF11 links alternative polyadenylation to formation and neuronal differentiation of neuroblastoma

In gene regulation, diversification at the transcriptome 3′end is linked to differentiation and dedifferentiation. Here, the authors discover extensive transcriptome 3′end-alterations in neuroblastoma, regulated by PCF11, and provide an interactive data repository of transcriptome-wide alternative polyadenylation

Triceps ruptures

Triceps tendon tear is a relatively rare injury. Rupture is often associated with pre-existing systemic conditions or drug treatments, including the local or systemic of steroids. Patients tend to be men who practice sports and are from 30 to 50 years of age. Injury is commonly caused by falls on an outstretched hand, direct trauma on the elbow, or lifting against resistance. The clinical examination may detect pain, a palpable tendon gap, and extension weakness, while a pathognomonic flake sign may be seen on radiographs. Magnetic resonance imaging is widely accepted as the gold standard to evaluate the size and extension of the tear: triceps lesions often occur at the tendon insertion and result in either partial or total tears. Conservative treatment may be adopted for partial tears, with patients normally being able to return to sports or heavy activities after 4–6 months, when symptoms have resolved and strength has almost returned to normal. Nevertheless, patients need to be followed closely throughout this period to ensure that the lesion does not worsen. Primary repair of complete triceps injury should be performed as soon as possible to guarantee the recovery of daily functions and sports activity 3 and 5 months postoperatively, respectively, minimizing the risk of re-rupture at the same time. Postoperative care is based on elbow immobilization for 3–4 weeks and flexion block bracing for a further 2–3 weeks. Full flexion and active extension are normally initiated 6–8 weeks postoperatively. The recovery of extension strength against resistance starts after 12 weeks, whereas unrestricted activity is allowed after 5–6 months. Delayed diagnosis and treatment may complicate primary repair and lead to the need for reconstructive procedures. Small defect reconstruction by means of the anconeus rotation procedure ensures full ROM and strength in the long term. By contrast, an allograft using an Achilles tendon or hamstring autograft is required in chronic cases associated with large tendon gaps. A long rehabilitation period is to be expected in such cases, and muscle strength may only partially be regained. The postoperative protocol adopted in augmentation procedures is the same as that adopted for primary repair, though each step needs to be delayed by 2–3 weeks

RNA-binding protein CPEB1 remodels host and viral RNA landscapes

Host and virus interactions at the post-transcriptional level are critical for infection but remain poorly understood. Human cytomegalovirus (HCMV) is a prevalent herpesvirus family member that causes severe complications in immunocompromised patients and newborns. Here, we perform comprehensive transcriptome-wide analyses revealing that HCMV infection results in widespread alternative splicing (AS), shorter 3′-untranslated regions (3′UTRs) and polyA tail lengthening in host genes. The host RNA binding protein cytoplasmic polyadenylation element binding protein 1 (CPEB1) is highly induced upon infection and ectopic expression of CPEB1 in non-infected cells recapitulates infection-related post-transcriptional changes. CPEB1 is also required for polyA-tail lengthening of viral RNAs important for productive infection. Strikingly, depletion of CPEB1 reverses infection-related cytopathology and post-transcriptional changes, and decreases productive HCMV titers. Host RNA processing is also altered in herpes simplex virus-2 (HSV-2) infected cells, indicating a common theme among herpesvirus infections. Our work is a starting point for therapeutic targeting of host RNA binding proteins in herpesvirus infections